Adult stem cells collected directly from human fat are more stable than other cells -- such as fibroblasts from the skin -- and have the potential for use in anti-aging treatments, according to researchers from the Perelman School of Medicine at the University of Pennsylvania. They made the discovery after developing a new model to study chronological aging of these cells. They published their findings this month in the journal Stem Cells.

Chronological aging shows the natural life cycle of the cells -- as opposed to cells that have been unnaturally replicated multiple times or otherwise manipulated in a lab. In order to preserve the cells in their natural state, Penn researchers developed a system to collect and store them without manipulating them, making them available for this study. They found stem cells collected directly from human fat -- called adipose-derived stem cells (ASCs) -- can make more proteins than originally thought. This gives them the ability to replicate and maintain their stability, a finding that held true in cells collected from patients of all ages.

"Our study shows these cells are very robust, even when they are collected from older patients," said Ivona Percec, MD, director of Basic Science Research in the Center for Human Appearance and the study's lead author. "It also shows these cells can be potentially used safely in the future, because they require minimal manipulation and maintenance."

Stem cells are currently used in a variety of anti-aging treatments and are commonly collected from a variety of tissues. But Percec's team specifically found ASCs to be more stable than other cells, a finding that can potentially open the door to new therapies for the prevention and treatment of aging-related diseases.

"Unlike other adult human stem cells, the rate at which these ASCs multiply stays consistent with age," Percec said. "That means these cells could be far more stable and helpful as we continue to study natural aging."

ASCs are not currently approved for direct use by the Food and Drug Administration, so more research is needed. Percec said the next step for her team is to study how chromatin is regulated in ASCs. Essentially, they want to know how tightly the DNA is wound around proteins inside these cells and how this affects aging. The more open the chromatin is, the more the traits affected by the genes inside will be expressed. Percec said she hopes to find out how ASCs can maintain an open profile with aging.

Story Source:

Materials provided by University of Pennsylvania School of Medicine. Note: Content may be edited for style and length.

Here is the original post:
Stem cells collected from fat may have use in anti-aging treatments ... - Science Daily

OSAKA, Japan & LEUVEN, Belgium--(BUSINESS WIRE)--Takeda Pharmaceutical Company Limited (TSE:4502) (Takeda) and TiGenix NV (Euronext Brussels and Nasdaq:TIG) (TiGenix) today announced new data from the Phase 3 ADMIRE-CD clinical trial, which indicated that investigational compound Cx601, a suspension of allogeneic expanded adipose-derived stem cells (eASC), maintained long-term remission of treatment refractory complex perianal fistulas in patients with Crohns disease over 52 weeks.1 Results were presented at the 12th Congress of the European Crohns and Colitis Organisation (ECCO).

The ADMIRE-CD trial is a randomized, double-blind, controlled, Phase 3 trial, designed to investigate the efficacy and safety of the investigational compound Cx601 for the treatment of complex perianal fistulas in patients with Crohns disease.2 Patients were randomized to a single administration of Cx601 cells or placebo (control), both added to standard of care.1 A significantly greater proportion of patients in the Cx601 group versus the control group achieved clinical and radiological combined remission* (56.3% and 38.6%; p=0.010), and clinical remission (59.2% and 41.6%; p=0.013) at week 52 in the modified intention-to-treat population (mITT).1 Of those mITT patients who had shown combined remission at week 24, a greater number in the Cx601 group versus the control group reported no relapse at week 52 (75.0% and 55.9%).1 The rates and types of treatment related adverse events (non-serious and serious) and discontinuations due to adverse events were indicated to be similar in both groups (Cx601: 20.4%; control: 26.5%).1

Crohns disease is a chronic inflammatory disease of the gastrointestinal tract, which is thought to affect up to 1.6 million people in Europe.3 Complex perianal fistulas are a complication for people living with Crohns disease and there are limited treatment options. Recognizing the rare and debilitating nature of the disorder, and lack of treatment options, in 2009 the European Commission granted Cx601 orphan designation for the treatment of anal fistula. In March 2016, TiGenix announced that it submitted the Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for Cx601, and a decision by the EMA is expected in 2017. Additionally, in September 2016 orphan drug status was received from the Swiss Agency for Therapeutic Products (Swissmedic) regarding Cx601 for the rare disease complex perianal fistulas in Crohns disease.4

Perianal fistulizing Crohns disease is difficult to treat with currently available therapies and often leads to pain, swelling, infection and incontinence, said Dr. Asit Parikh, Head of Takedas Gastroenterology Therapeutic Area Unit. Existing therapies are limited and associated with complications and a high failure rate. Cx601 may offer patients an alternative treatment option.

These data highlight that the efficacy and safety of a single administration of Cx601 were maintained during one year of follow up, said Dr. Marie Paule Richard, Chief Medical Officer at TiGenix. It is important to also note that the definition of combined remission used in the ADMIRE-CD study, which includes both clinical and radiological assessment by MRI, is more stringent than the criteria commonly used in previous large scale, randomized clinical trials evaluating perianal fistulas in Crohns disease, based only on clinical assessment.

A global pivotal Phase 3 trial for U.S. registration with Cx601 for the treatment of complex perianal fistulas is expected to be initiated by TiGenix in 2017. In the U.S., TiGenix intends to apply for fast track designation from the U.S. Food and Drug Administration (FDA), which would facilitate and expedite the development and review process in the U.S.

Takedas Commitment to Gastroenterology

Takeda is a global leader in gastroenterology. With expertise spanning more than 25 years, the companys dedication to innovation continues to evolve and have a lasting impact. ENTYVIO (vedolizumab) demonstrates Takedas global capabilities and expansion into the specialty care market in gastroenterology and biologics. Designed and developed specifically to target the gastrointestinal (GI) tract, ENTYVIO was launched in 2014 for the treatment of adults with moderate to severe ulcerative colitis and Crohns disease. TAKECAB (vonoprazan fumarate) is Takeda's potassium-competitive acid blocker and was launched in Japan in 2015. Takeda also markets motility agent AMITIZA (lubiprostone), which originally launched in 2006 for the treatment of chronic idiopathic constipation, and received subsequent approval to treat irritable bowel syndrome with constipation and opioid-induced constipation. Preceding these notable launches, Takeda pioneered gastroenterological breakthroughs in proton pump inhibitors beginning in the 1990s with lansoprazole.Through specialized and strategic in-house development, external partnerships, in-licensing and acquisitions, Takeda currently has a number of promising early stage GI assets in development, and remains committed to delivering innovative, therapeutic options for patients with gastrointestinal and liver diseases.

About Takeda Pharmaceutical Company

Takeda Pharmaceutical Company Limited is a global, R&D-driven pharmaceutical company committed to bringing better health and a brighter future to patients by translating science into life-changing medicines. Takeda focuses its research efforts on oncology, gastroenterology and central nervous system therapeutic areas. It also has specific development programs in specialty cardiovascular diseases as well as late-stage candidates for vaccines. Takeda conducts R&D both internally and with partners to stay at the leading edge of innovation. New innovative products, especially in oncology and gastroenterology, as well as its presence in emerging markets, fuel the growth of Takeda. More than 30,000 Takeda employees are committed to improving quality of life for patients, working with our partners in health care in more than 70 countries. For more information, visit http://www.takeda.com/news.

About TiGenix

TiGenix NV (Euronext Brussels and Nasdaq: TIG) is an advanced biopharmaceutical company focused on developing and commercializing novel therapeutics from its proprietary platforms of allogeneic, or donor-derived, expanded stem cells. Our lead product candidate from the adipose-derived stem cell technology platform is Cx601, which is in registration with the EMA for the treatment of complex perianal fistulas in Crohns disease patients. Our adipose-derived stem cell product candidate Cx611 has completed a Phase I sepsis challenge trial and a Phase I/II trial in rheumatoid arthritis. Effective July 31, 2015, TiGenix acquired Coretherapix, whose lead cellular product candidate, AlloCSC-01, is currently in a Phase II clinical trial in acute myocardial infarction. In addition, the second product candidate from the cardiac stem cell-based platform acquired from Coretherapix, AlloCSC-02, is being developed in a chronic indication. On July 4, 2016, TiGenix entered into a licensing agreement with Takeda, a large pharmaceutical company active in gastroenterology, under which Takeda acquired the exclusive right to develop and commercialize Cx601 for complex perianal fistulas outside the United States. TiGenix is headquartered in Leuven (Belgium) and has operations in Madrid (Spain).

About Cx601

Cx601 is a suspension of allogeneic expanded adipose-derived stem cells (eASC) locally injected. Cx601 is an investigational compound being developed in Crohns disease for the treatment of complex perianal fistulas showing inadequate response to at least one conventional or biologic therapy including antibiotics, immunosuppressants, or anti-TNF agents. Crohns disease is a chronic inflammatory disease of the intestine and, as a complication of it, patients can suffer from complex perianal fistulas, for which there is currently no effective treatment. In 2009, the European Commission granted Cx601 orphan designation for the treatment of anal fistulas, recognizing the debilitating nature of the disease and the lack of treatment options. Cx601 has met the primary end-point in the Phase 3 ADMIRE-CD study, a randomized, double-blind, controlled trial run in Europe and Israel and designed to comply with the requirements laid down by the EMA. Madrid Network issued a soft loan to help finance this Phase 3 study, which was funded by the Secretary of State for Research, Development and Innovation (Ministry of Economy and Competitiveness) within the framework of the INNTEGRA plan. In this trial, patients were randomized to a single administration of Cx601 cells or placebo (control), both added to standard of care. The studys primary endpoint was combined remission, defined as clinical assessment at week 24 of closure of all treated external openings draining at baseline despite gentle finger compression, and absence of collections >2cm confirmed by MRI. In the ITT population (n=212), Cx601 achieved statistically significant superiority (p=0.024) on the primary endpoint with 50% combined remission at week 24 compared to 34% in the control arm. Efficacy results were robust and consistent across all statistical populations. Treatment emergent adverse events (non-serious and serious) and discontinuations due to adverse events were comparable between Cx601 and control arms. The 24-week results have been published by The Lancet, one of the most highly regarded and well known medical journals in the world. The Phase 3 study has completed a follow-up analysis at 52 weeks confirming its sustained efficacy and safety profile. Top line follow-up data showed that in the ITT population Cx601 achieved statistical superiority (p=0.012) with 54% combined remission at week 52 compared to 37% in the control arm. Long-term results also showed that, of patients with combined remission at week 24, a higher proportion of patients treated with Cx601 had no relapse at week 52 (75.0% vs. 55.9%). Based on the positive 24-weeks Phase 3 study results, TiGenix has submitted a Marketing Authorization Application to the EMA in early 2016. TiGenix is preparing to develop Cx601 in the U.S. after having reached an agreement with the FDA through a special protocol assessment procedure (SPA) in 2015. On July 4, 2016, TiGenix entered into a licensing agreement with Takeda, a pharmaceutical company leader in gastroenterology, whereby Takeda acquired an exclusive right to develop and commercialize Cx601 for complex perianal fistulas in Crohns patients outside of the U.S.

-Ends-

____________

* defined as clinical assessment of closure of all treated external openings draining at baseline, despite gentle finger compression, and absence of collections >2cm confirmed by MRI

References

1 Pans, J, Garca-Olmo, D, Van Assche, G, et al., Long-term efficacy and safety of Cx601, allogeneic expanded adipose-derived mesenchymal stem cells, for complex perianal fistulas in Crohns Disease: 52-week results of a phase III randomized controlled trial. ECCO 2017; Barcelona: Abstract OP009.

2 Clinicaltrials.gov. Adipose Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulizing Crohn's Disease (ADMIRE-CD). https://clinicaltrials.gov/ct2/show/NCT01541579?term=cx601&rank=2. Published February 2012. Accessed February 9, 2017.

3 Burisch, J, Jess, T, Martinato, M, et al., on behalf of ECCO EpiCom. The burden of inflammatory bowel disease in Europe. J Crohns Colitis. 2013; 7: 322-337.

4 Swissmedic. About us Collaboration National collaboration Patients and Users. Available at https://www.swissmedic.ch/ueber/01398/01400/03296/index.html?lang=en. Accessed February 9, 2017.

Original post:
Takeda and TiGenix Report New Data Highlighting Maintenance of ... - Business Wire (press release)

As a boy growing up in Nigeria, Abba Zubair dreamed of becoming an astronaut.

But as he prepared to apply to college, an advisor told him to find a different path.

He said it may be a long time before Nigeria sends rockets and astronauts into space, so I should consider something more practical, Zubair saud.

He decided to become a physician, and is currently the medical and scientific director of the Cell Therapy Laboratory at the Mayo Clinic in Jacksonville. And while hell almost certainly never get to make a journey outside the Earths atmosphere himself, if the weather stays good Saturday hell be sending a payload into space.

A SpaceX Falcon 9 rocket is scheduled to launch at 10:01 a.m. Saturday from the Kennedy Space Center on a cargo delivery mission to the International Space Station. Among the cargo it will be carrying are several samples of donated adult stem cells from Zubairs research lab.

Zubair believes adult stem cells, extracted from bone marrow, are the future of regenerative medicine. Currently at the Mayo Clinic in Jacksonville they are being used in clinical trials to treat knee injuries and transplanted lungs.

But a big problem with using stem cells to treat illnesses is that it may require up to 200 million cells to treat a human being and the cells take a long time to reproduce. Based on studies using simulators on Earth, Zubair believes that the stem cells will more quickly mass produce in microgravity.

Thats the hypothesis hell be testing as the stem cells from his lab spend a month aboard the space station. Astronauts will conduct experiments measuring changes in the cells. They will then be returned on an unmanned rocket and Zubair will continue to study them in his lab.

We want to undersrand the process by which stem cells divide so we can grow them at a faster rate and also so we can suppress them when treating cancer, he said.

Zubair became interested in the idea of sending stem cells into space four years ago, when he learned of a request for proposals that involved medicine and outer space. Hes been trying to arrange to send stem cells into space for three years.

In May 2015, he sent stem cells to the edge of space as a hot-air balloon carried a capsule filled with cells from his lab to about 100,000 feet then dropped the capsule. The idea was to test how the cells handled re-entry into the Earths atmosphere.

It turned out well, he said. The cells were alive and functioning.

Zubair was supported in that effort as he is being supported in sending cells to the space station by the Center for Applied Science Technology. Its chief executive is Lee Harvey, a retired Navy pilot and former astronaut candidate who lives in Orange Park.

While stem cells have myriad potential medical applications, one that particularly interests Zubair is the use of them in treating stroke patients. Its a personal cause to Zubair, whose mother died of a stroke in 1997.

Weve shown that an infusion of stem cells at the site of stroke improves the inflammation and also secretes factors for the regeneration of neurons and blood vessels, he said.

Zubair hasnt entirely given up on his old dream of being an astronaut. Hes applied for the civilian astronaut program. But he doesnt expect that to happen.

Im not sure I made a cut, he said. I just wanted to apply.

And he realizes what a long, strange trip hes made.

I have come so far from Africa to here, he said, and now Im sending stem cells into space.

Charlie Patton: (904) 359-4413

More:
Mayo researcher Abba Zubair is sending stem cells for study on the International Space Station - Florida Times-Union

Stem cell therapy treatment gives new lease of life to 5-year-old Jamshedpur February 17, 2017 , by Desk 1

Ranchi : Till very recently, it was believed that brain damage is irreversible. However, now with emerging research; we understand that it is possible to repair the damaged brain tissue using cell therapy.

Again, today there are still many people in India who have not preserved their stem cells through cord blood banks. For all those patients, who have lost their hopes in finding a new treatment for neurological related disorders, adult stem cell therapy offers a new hope for such kind of patients.

Dr Alok Sharma, Director, NeuroGen Brain and Spine Institute, Professor and Head of Neurosurgery, LTMG Hospital & LTM Medical College, Sion said Stem cell therapy is emerging as one of the newer treatment options for conditions like Autism, Cerebral Palsy, Mental retardation, Muscular Dytrophy, Spinal Cord Injury, Paralysis, Brain Stroke, Cerebellar Ataxia and Other Neurological Disorders. This treatment has the potential to repair the damaged neural tissue at molecular, structural and functional level.

Dr. NandiniGokulchandran, Deputy Director, Neurogen Brain and Spine Institute saidStem Cell Therapy (SCT) done at NeuroGen Brain and Spine Institute is a very simple and safe procedure. Stem Cells are taken from patients own bone marrow with the help of one needle and are injected back in their Spinal Fluid after processing.

Since they are taken from the patients own body there is no rejection, no side effects, hence making SCT a completely safe procedure.

Today, we are presenting a case study of Ranchi based 5 yrs old Master Dhairya Singh. He is a known case of brain damage due to lack of oxygen but not during birth. Dhairya was born in a normal manner, cried immediately after birth also his birth weight was appropriate.

There were no immediate post-natal complications reported. Dhariya was a normal child till the age of one and half years old. Then one day he suffered from an episode of pneumonia for which he was hospitalized for 6 days.

Last updated:Friday, February 17, 2017

Previous Article Rungta Mines launches computer literacy course

Next Article Jharkhand to see investment worth Rs 55K crore in highways in next 30 months: Gadkari

Excerpt from:
Stem cell therapy treatment gives new lease of life to 5-year-old - Avenue Mail

n}"Iu'.-[@$(~I)/NNbr.PBZ0R W.?ry3G|6EABWfShU+3W31@L-*3vf ~nQr1AsiP*T Qhn8EyR-^B_V|,9n )GI^chn0ZZvu9Ri}Z $(_*](u"&E1.LgERi#A,lq=&giZpx6f,dq08qsJ)rsFhW?sYL?OCL?X%81nUua*UjVMw:S*zL"BxLM"x}Y%m~fRRM)8#Y%cQHF#Y,P_g |.e&( 2A"d>WU23%0T'( g,,Ms3#t,QIf2%,TE2 , |[N,)!a7<0 2?M 4q4H)dc2 ,J y1F,J_B6dd4%OX3wh$SdcF~j4 f$gnd$~N6W-+r?+XR2? DI4Bd~4M)!%/GZ}u1x@D@~z&Puc/~%%D&1<"$ hQeE[Q28G0 #J,(u3"y@58p]0fuOeB_-gGhI8)Qv!1*y@O|I(,d!ei*'i&O;%dn:49qf %Ju{ 3pmV29_ 0y{*ZR}jT;2}2lekF;*S21u&Nm*Xe9-< P-A+?g`B7JOj}tu,$o!8UpB#WmYMU.l1)}SsXftR?s:LSpdy$icRtclZCPun A.4,e8.=V2Tk@5%UT`u7~cQC7RC'wCj.GG|$NM &2o&'^MO7t; Rn]2lrdup]wzwkG{Eyq*94r:_4@tS@ml1<-Z*o#y8 Wu}[7dj7GL"_5Iup*X9toEMD[Yo8+ `|$Pd,ia/CR<"@ K"9CHJ}]P(=Y $#fXAfI#WqL2F'(TSSxx"<0ETwYVq)ZL Eak) 2xXb:D<`!bhDFIH>^C;2hy8X&M3SzL(X4=GlIig.!~Dr6#}kpbnds{>2J%E,5 ."[m.' 4]_`sn? v 8]FR.k]@m}q{x`Gx^D"(r?d u[vd]7fn?k;Y1WZc$#9]VP$bqz/~:3m^FpO !UWTPC{ Bcz&u.X4h'uj%Gc4fd 0&WRY"YSP7Pd=u<{5K)?n{IbPa/Q|Ay90'7wzF,Col~q8LxYcU"Fk.x*7ZmCm%8z%DLq / hDW@Y$:]e&Ha{'zmj &iW(@-/JoX`=2DH/DT5E0/CLP^_XAK;6)f_]KO0+*bEBM{/mT[ jLGY@i<~M<36l"yM[z!lf)>W.qiYH;M :V0Oqs!k:%_}Z7k]% dB!N:Fj|o jm8P{+u O !t%Pih/] @8i*I+yf^QbS58V;NXoV(l*P<`jGl.jf@G -O^rSO:X|*Gs77UN!g}%^f'vHC'$cXL0>XqZCA|$+x-`UNy:ms -25p'mCU}LGVMi4'"`2;n/Jh6h/u!yXIXA FKf,"Y}n}"E|SO/Sj?@io:Xc4A7(h.'nha5wq3iT@-Q{|1'p1x4RfFZ"Or-DZU+= !+X018=~chAn",f;Y&y{r|[M!XAm3 J}1AQZ4]]7/cBKEmD{6OAw8<<"!oh~nbwO7n:Zwl.|.XIv"6KY]o>yU_"-"RMr0^ Ktp)ex+Q >&k(SH@d5Gy%,jB*!>}F)bh_ky>_g.&~9gOiG$|tXA<]j09A`Bz;+6)#j-q>ty5l\tS#A]{G;|>m,{>K|^un76A3LK>4|+2xCZy!d[q8GJcxoM9M]_S$nH{l8TTUxV8WWXCSwkBk@g#^O}R)KDPHo43Ao2)8}I I}G=*/dV)'fV,/ ]Kj@.`a?cv}q)8'R(DFIDIL43#Nd3c8I83wt8B!$I3A=w:NfMMz tr{sH `!W6/_FtG*HJ2[Z+l@/8$z'w/.)1~x}{O},U"wxBT,)"Iwv&s n*]Y3f_dagr}CJI7m)rgZXK{o;/oRc*HH{Ox rpIcetB@p>ggS$|O0^q-7/7L|GW9rB`08v|O@9Uq,Jj]QfiGlgjxT+I9g ~`J/HrBkS=+J{Xd`aN#2[YT,n5w"i$f IF 8hEiPUF&eLw;@Ici5Ck2k81nQ$BMb/N<"9*Z Nq"`R5_f~/VavRq)=(Z]KoD+88qA@hHnd'`,aU{ydAVe~UWG?==r7N{P|Vbh$vw*Ov C]bKKFOEo`R|s}rsYTrA@twa*?i~wf|/wW,Yl IYN=1ND.|tc]Xkx!= >_}w1Zi:1kC;fG|cy SIKw(w{5_7j_8h_WPBt}tz} 6igh/*1TM=gjka[-3 }Yya9u>=NL5&t;b71m+xx=vpyy?P[a.&aF<)__mnOL[TB[kOW!v:r7M[kq_4qH1FSzY_1)Y&sy6yFRgy{; $7#&KTL]H/|(}Z"s,{Rl.n}xcf&9*9D{q{DN]]W0HqAB/{YHsZfW/7~W[f2q6nD/_w6/$iFnt9'riXF"Mrpc9&[ecI>#:G_N, v= y-N< Y)dw,e&YqM~tQ"cn/;.>6Y'BXHQ1.H#XmlB^RLM3Clw`#R[+8H"8,y +|l`${ EfXdTlFtsB{4,Z`cp4Mb'+fp @*ND)Sm??cT8R#2wV1k<>3 9xy qI DxW.K-~-%VtG&05XNz+W 5>'"T =1+f?pbB3*;0 5Z g 'jrnob }@wDk{#PN,3N$>4DFG;6*LUe]bBd2UNU UC3[6p%nY#@Q]D5:`dQ`'uc"7Nnifc=DZSHaE@yu mA%1R;CuIXt$V"[a}1./PU9(s!,vX$/(Aa%YLFOP pc6S{MHKx|9@,7e3H7:M7K^N!9Er6DjqjS7^T.Bz~,)qJ/:z?NSX:Qu@ akFL(,'$B{_!hN;qx )T8jvX,x?|0M(*I+AER`,lP#g(cP"$A@7tkTf`"G(Tq2j C' rNs}4Rs%` 7KH2X'P*AaC-Gx&6P`/,29-k00rFOtfzDbLQ^(F:NzG!BMS>0 hL`Rv#;m#HS_// Efg_DH9UK18^da(/tu:dh}H@n[M=_Ag 3X]HMKS EP&3c5LrLXT0i=Qz{`yfY iHHZ9< @qJi m'|`~)uWQ/~9?w:7JJ"#U];?/M"-7w')o=@VC4k#%mC-}}1(;I!.eF3KuJPfs8qn^uk1[7f5z(?m\Ch:?GykWU.=V~cyo7eq?%}R2}"]RzYjo+enQk`y&LfiB|! {^jh7j>uQ=^x; >% TlfcmX'5Bx|`!4j5AQV#4a($`*iQ/%][$s4.wV]"Ic[!8wk2_;H5]i9yGYjI5Lfu ^/z. oxLAMBPu=X"t]]C!{Kd{E*<)U?MoqG~N4W75=N,_|~H+>_>"Sj[CuIIa$;wW2>M- 'pQFZQKEl9Ut qX?H3Su `= (qY b{st$9EK$cnL1J7-YjM>{bT-5i+R0NfoZv ,Iv$h&jn"Ar2 `|B$.bPR94GfEO(oJQt%R&6NRZ@W^*h)m"HgJg)A&Q8hCo8n1`lZyS|'hTcV]]2~btE&4OGK.kC; $,l`Es!nM,I51P ek"[v+^4l.c5Z9ZP P!{?MnX H]un|{[lo 1z?,Qs 2C}k9|5D<>]FUw:5=*i?s/nIE% z5vhh,4[qj;I`4+3d<5(Df29 7YOG$zW:z{lcgQe;h3@g9S@GETq y"Y"{SS!<-Sr=U.l,wn,"vJIT=R6"#0''m2Q@6?y$xEJfB @%W!E:e0rd&Xj r'"=a ;$11w> <+j-_G+;|PDp8gq ,O,dpxf) +li($;p,{h8S22Nl2'6&/PEqOVjbM0.-fbIJFeLKh*_>@)0R:ngDPRuH2.T9vA7gTv )V K{fe1+UeX)TaV[VtKTs6OT*);eqrvdf0fh*ZTUVI4+kI;aTJ/~K_ =MFMS_9xBr1?/*_?DN 1$fN&O.M>A9eOV_W+^:XS/~ZV}`<~_jA[i ]EqifU3y?O+k./z&1mu[<5X._="rHYQTHw*{a~_PtsDU7PISpezn $ &?*ec&r3P-.bvA6Xd(' BuJT3< +.iQ(~a`1xZ2jkv3P2ZjME2u9`=E8$tQW P`qW.x`dX>L1!~%6n;M{0-9z?hN_F^M:.:y!d B@i-Tz=(h*uLm*N8L5Q}3;t& <.IT5T<]._o ^BzMF;+&ei$23X2:|TJJUpSc'*$ Vu943<$ v}mlIvU8@=,^SIbVj-SSUMK3PuwZJ+&W=L!GkvupF|**/9X6NF"xtUIiA:2`/OJfthoVB'u DaF+iF3.ft6|>WV|HnY1}!!+aFJ>bU'@ox1y'jZ2=LhDftv!OvYu=3Zr)6_E/@D |};OETe{eFbCPl"n$.iK7z69V6F6R,tl%yDYhECU[(FDb]l$yPt,YQ.'MAB>ltF:TtJn!ka>y^hT"]NP:khuFm?XyZ27oKr5o`4>FW%xs jPc"#6WnDA ObN9jaD/;ooa2|2*(OS6!WUNY`&CWUP|+$_A6XYQ%.fSm']"|>A4d7FL]T,G?d0y++2H3H0l` BKXhO*Qp-TZ[7mo3Q""8kF"e')L-YTQyzq{*4n wE+'9G_Vq B1Hk]2S=+*S)?~ p$/|-1B. 9}=*!6=pHoDdE5!MT_KXF0q[Bg31p>hwuPX5X>zp PMy()T"lLzRkJH}0)W+WZ F1D]HW0'xU5Z @,onoDmP:*7TL.Je<@ `1z57b^TGWMe k8'#?fCXu'5KIFED__WeIsolglC,gNaQ4> 8{|viq>Q>2f1t_b}?oy{6.}`/cuW=hp),& C982dmk8Ct!-a]1_mv)x )j1 #nB&k_vVs^{3g tJ$v}2)BX 7 :*kq5Ulufut}6+`%SX8rQ'<;sm|mAvO 7I*t&MSa0UGqv"i:8Vb PZOk VAM8hR+W+tLj?DH3G)mzmAuSld ,QuUc,cZHB4x>=pZxr{1''Q{$xRL+lhgD;JW{%UT.V[32w0N m8"#"6R2}5N=?Qe6c#sYr6J_i9*-rum:/vFIs^]V;{_d$s#j2Mq}s1 |$XblJVUqw~@80"(df `Pd`-YOz Kx?]K6 /@CW59}MYTe'D@C23 #[yl`[C"F8B^P"-U||`8IgiY| RoKNl"o:LQ$+qVy - ^Nv3ydq6>(_u=vOa)1U66=FYH@bM1v?Q-2<3Tkeh-*B#]$4 &'|Xhl?)!V96@k*L4X1Uh{q; S'k_NY8/zPKs*\f*P1#IZ}K@"jsuD 26Wl*DQ|DCN@="N>jQ|Y[ z-V8;9{:U-zB&a9"mD>6GF3Q3n~b,|zImE@(.o*{d%Ega{4W1(F-sx7&VI9j !1=$ 0f8%}u0/-SX#-lR!PdUd8GyKX2*'iZ(hQK90WTGq!E1B^LKJ[B}C (X-THfp}I`n}e4 p2T>]rBlD~0),BNJ'U!!&eIwC#es /FWQ 2xH857G@KFBs=_i!o Ff^Q_1)'$^'V.^iq,;mw59mAg4bDDO`1vtPVhV]Q68m{]a,MJ` COzQTMR#>BKT-~8tI$G'P|>Z`:^"(!B1A)-0e*oUYzRfFHX`Ew ?:*G!9:V_qoza,?Co@1+YPSmQO~g;UHJyv%7xSFUg5%*ub& 8888)rP`G:E5Oo:h3rI gg;!dfyg@XbFnW}5J{NNZqxGPSAhKvYn>ZUI6;rauicwxU,rCAuAefi HiJ%08 P`7UMZ7S51[.tT&VAPjex *"qu~ [qG0 @kW?^Fy7iO]@t>Y[7=#}g `2Dme.G=NE&DU5Sinh@ac)V9Ad iNv2FCvjN93ln%+`8/)$];/_WF:5^[!CL2=sj@ B@:%71HL).MK^chJZ+#Fb;t`7SFj Cb#h#:q&+Z!f~ {4@v h^6+PlS;,.'Lf *^Pbt-<_Z(1~Rx<&a*x=6f2p_=GVC#i ~=#,C-bN9$ujS{^OSvEr%9h.Ypl<6T`'{%e,X56WPr@%}_3oe 1sJQ+myq'W9WDhP0{MNW~f1rU;J_,px G>mT~59roH3=;VdV7H =4[6g[htcH!l@`zL8^raummY}#o4O Fk#aMWrxJ+nuBP7`V2 !cI y}*!PDQ8+)y@``~;_M(,X]]f%X~V!]>l#>ObT1+ [p9,Qu~Fu_>nr}g3 q}U7)VE;3-b?3;C}3wT)qsri wz+d8P< %RDtk4$qY% XtAwwZ~*&5{41$k:!2%){V .{EpLA>0?sB_$m^{k_S$OvQWOPOyA'2'M s8ZUxJ2A_$=.mbj9ao}9}ZgndyrRjXGq{%ax ItR*4A Qf_76 ~{(H29l$Mz<-r*<(?f Fyugu~)89xHq_ZB@x8`RG;%GbSEg6i"SA_-&S_#WU;WaZe$lv>k[Y[|"o86Ni|[&G;V=}Rd245oB|R37] z6m;9v*/-;%yRLAs!u!bT[PF0 T;{ZwrX-**EVm" '3:j+/;JVS,#l3BDnT?vpC~ns3jviXaxnQO_lPmyo] hLOeM]ZM3FG97ekD5B `JF(p4jUy% H32jeWy>ne;kbCtG,)#H3H'h}UxA^KL';ZllNJh$Z:+::/Km+C dl*V)sa7+i&0?FelTMVo_FAwc4"zm"Dlj-]78e4"h,dy@?7o=k[?9oG=}7}?9eHDDrH : lmfO$`HasmT130Ma,*sD:=-cc"v0<|D`.`4rhpWb %&I! ] lH;3a(Kshtp9ASe.DKsUYn?S>m1

$F4m:s lTt+3}!YH6p4-eBv)l%L G!Cifm:!6!@@ULV^Tojx7eHu4M|]EM'R,+J& er:;9}"QU_c29Cf[RX?$t&M-+#' j'Nnu3i+cS"'52ayEZlSxSR>l:>/#TtuuUU?);sflKScU&2MJ#'(;w2 yEH3_ vKb(hZ~aM>#}-7HnrFpFF1 k79$dT TwzA/,2fyA3P}EFpdf6qu|nqqJOv9~UE1*_YC% @Z8!1m qan*2Ra+O)/oq~KLSuYaj1!_MLP~- %f!c v2Ss9m]~x }obnt4pO.6qmT,$Z~0aPz($s3`th=* J5Dg6nocay[=p"?L3zKt <0%q?h!mC#G+Mr^oVv$KE^H{|UW5Z5pY b-e4}h0=N$+5R3W)3D'/UE=#JV(Z4a!BoK&3xN>c%#k# 2g~ `cTm 2J"!l9"r<8HJP!nL%)u{{dk:O|>7hlYvL/T,B#8*g)*9lz0@q@o:+c'"7 aVF}K[bzSPFwtT!ll:"dr.On#axQ9}M9t2/nFX;e2lqVp"5,cRzohH25^ U ^: yZ MAq,ii]DZ{rFgN?BH3BRLZ-N3PqwTgADw>wThYoJK[CJ^MYE]57)Y( 1/dNm5qBVk|yI>5he; y_NNaKPiiN@(^!YIZV_x43- A@XIAxu#~tY)FeTwT[c>Ve9af8gF76z[P4-+)9FAB9 Ro*k;TMFcKz>aX R?2l=?K{pbh`bG_yF:xgS - {?A@cF3y >DX/f`fCCV*F1Y+B/8U*X/~%Q]/hz` Hj"~2gun-H+W"=wPM}=L]Y*J^@:i,~df?K-< I)}@0A }n+Fh1r^|D_O>>m1Qirh5.=ltMe!)IJlDAz"r-<,uhQ|ThMh6y,5Om;hK!h>T[Pv%U)S]LJ2dmnk[R?BY@Ed{jl v`]oz{4ntn&~;/kQpu>Kw@#[u oy Lt;CWqUF[ F ~&E}0)`^ *"n3q.Cp1csR;=EQ1o<#KS8hv&&tU8KU b-K`7R'O uKW5p_2MpvclnC7z8+($ N* yD[bjq >pYO#Ob{JA~kFe1S'by"lNz9%T.jPO0eIv.bN$S!>dr&4tm?Uzc=4bm?a|h.^C!xS)7s%Lsb1>~_hY~PIs]BZ0.BX(yfbHPPB s$Ux'*a+/93Q~pQx"rj|Mm%;Eo7efRg?h~2%YYORh>|]I6>@E(uD@R&). JmqF_?[b&7AU4j{/"b+0S%2I=;zi]eU_b7}.1&%:S^8w @lG^g;cW"/fntins"Ni*L |:^WJjx*;(+SWEy^p3uFYw.fa`R;hj2aVrMm**fd nv)7} q?Vsj%UIeyXN<*LT5h`J=X'nAE~lcAq0E,Vf4AZx]kv0+M>;F/j%j&p%yyG{5dI1nuP5Ec{elTlz.A&Au&pjNKyq2[.w>^c-,L$&eM{;%w~xF!/he#Q]`'@g(8^aC4=6|HBhnS y7 d(bn3bTwA(hZQ "GchMeW'5I003CUqF^h*]~#v]=p6FZX(Z=3~%zs{p(,lu5:X:QsZTBTnZ+0"@Y ,$&x OAZm>_pJP|y;6wTgHtcL9bn[2K0>ou |%9.qt/jG |@AP4,&+} Q.lDPWVzLwac{uWg`?s|NDzby1/?[/]"A/@ }nw}FVYY!Uebqp8T[+8yHfF8S4I7) {P7&0Mg z/7']nF|f@1FFH{%IF`` kf]{"@[o5zj4"s Y`p3aWSd~>=DN#]^`mlkKVnwP+q_"7}~ayAOhl}_Q"Um_39Y_[k*Cb<@f;K"(690cbU&Q5o@[3#kj805o*3tw+QDVH';!VM@Ru"1T5tTENE%%S<(!nb9+H^vx>AZ`@wb:|y_w!;4xljFt # o]7nD]a.A+wOZXic_PGWRD txA/-6gM.%49h3m"XZ}QdybM L (ichkrs(Un0v%VJrZ}qRRM#BtkJ!B}eXPVR?n/)r-i=~z/&<==qyX%k6o-1K)'u)erhI9^K)4O^GVR_ax9y%5_g1EU=e7bWB*~ldNzu2RFOZOmOj|S+W&.wWX<2r,2tz}'KR*ej(< R}/eGOyQ$6.GC2N?,+jTW2B_[s<'O17h*67'p+hzmW29d9i>^<y]@;sP}Z;RCd (bk@Ja5

<~9Q/CN@ %G!kvPXrJMQ~Z"t~sMmLXpRzv78UUr * }RPN*cN[MPz%JTc6u|QuBvXE- 1GxNP03L4G`/Whsp =_:g[z_%z12"(}= AO^Elp|V.d~ M[(2j'='Jq&pT3zs)^3/Pa=-C.uo'8E7W[1&Vn s)2vL]VHC5u7dtfQ~{>V0 NNQNhu17*9&_^>5!EP5 mk`Az/<{Rp3Xm5@@3iJVD=d@[`^+UE+-;%%S_D'H@|n*&(@V{I 7f:^;7t4?7U|C 5__>TGW_^g#zhlZQ rL;M]%5sE~ZkzM6vA),ji@Y(}8cM%GQ{CoW/{0''n,`e)Pp[1;}leP'R d/Xq*83;R][o:+f]t_,e*K8;ReQ4@Cr883C~j?{2'Zt1Gb s.8~X]2'"W _arr{C)FpNIW1 3ufk%OY,_?4['?zJst% !I1# ^u(|,$AWbEqJ:p ~+B/p;JkPq;vTY,K['yaQN:cXUk>;r.M.r`xYK^$-WNOHB6,keiM[;.%|[o]h 9l;8pW]yNcz1D-r)G*K`HHHMNpoLHhRR;B+W^|$|PK|3t[3vCPh3 F!&?8;, SfQW| !0#_b5Fg[ Bu{'#:Ux/D7Zt/A3<&>DxW_H(%y:8a!L^!Q 9pM1;)=xV-#(qXlnnwb_k(nmJ4m f K} _dPt'yUeWLlxRRm~PgUL0i.Osmby<2*:),a:LL@C)uD r+i,T$f:3vF,r]aHYyie.c9,.3D3^'+/7]AU)Q5@suVvMZ@'}Osw=P:.k~1ZAszv8]4h(wMp `t=XTBkgvu#CH.X |ewEi*4 m*V/Ae1s5Z5t$wPvRzWu9@oGug,:XNd[@75k,x=PwM1pk.;{tk>1w2H6q`O= dag TV`2@^kjGW?rp1yu;e${O|XGun{~Df<>DS[[sJ+~9JL `Dr1"X8%(Zht}I_rv/DfuL%4L.I>NN6yTwwvtL( c8}~xvO{. }qBw*T_ytguyt7i@tB ;^wCT:7{]2Y^KcW_+^pb.6~zL;uE5ZwbO1wC:yO>Y(u1_/G+_2M}0.:=hmQ13Y}HG[co^?|g~[F"4Dq'dK,4b~atgJ=]YA6%r%2a[3`]ZyVQ%OpkuCG/) iTLc,!vV> Xd>vPWeTehm-"[{{ ?3c}|Ojcb;!?FcyBgk?H_{/mMmlMwCzlgmdE{6^W>[u{kgwpp9%Cy 8i11 H%R;g`KMgr{X0 E '1GW@1-lF%+39->0di `/e'a ~*H ,$2}"CO]E=oLIcXI<0&;%t~HLN3;czFUBk;.N`<1o,iBc7ctKr)c0L!$w=.GHC SSC*9"aXrV6_3>?2xharBve[]kVs~#W1y dC @pQI_jR#A*>, Ny/Fr9$SX?& H>|n$6|g^Kmqrg)X#fl8pi>r@3Y]+kfN9oV1!1y["DN&59-C}+ea#,|TWWVper-^Q7inlL7RWox^%M}`sQ40!R;LqV$184#K`0I$00T=[~ 5]*[;.~i7Aj(m?Cbl238[y lgs, :Wbc;v]cw_Mbts"P%#umlB 6+g)r.8_jcI l+ruskQR)F[=Scq%/uc|Sq2u; z1qu@ Wol])2Dn^G*{~36S~~%?IQlU Wq}ccmO9XwvOaZC>4g9~7Go]6 i^Xf_^V[/{q2u^ ;v,/7=~/?l]$.KF]n/{-y&h-CcB:odOs^y9B_U~Lv>}MO75cO7]{f}Xoh&?7GO]yJ :;%d,x5%B$W@;Y^+)>r@!^3Wuf2LSX;Bu2]^LZ(o8M9@Sg'Qoosr]SH&Ira8VePQX4V*:^^P .1cjgqzHC3)vh*Q1kgg~7Pu_Q#B6@uqt&~}?bP vO?:Ngy6Hq'Wx Y h#$!@2<}2E}:;7x7LH ?ruR!g3su?$PCBcAnxwhRvYexlSrY?eNA~maZ.p5|Y+*9sO<_IkR;||q|0R'*[MyYVd%x4Y?vVAoD@u`-fcp!-}2%`4W~ 4c++:m,Hit_m9jxn4jj xS/ zkmktE qr9)' ah .Eup,-2}mpnL>71E5UJF`Cviu~Euc`Io"wN~I*H_]n0rll/wFJrrKb,EP~TvUEU${]`-@<-: t.mGp:17 yZ7 35DBQSY?yodJUQyK3 =TlPij~q9tTz0^6fAD16iT0^F0IrVL!;^_g5xTv-|*hJ'9Oh+D$k%0.d!X#JX3 kU=2.&KruF@(XAn?J, #fzrt }Dm)>_(.ZalT^#NStFubb2b]ev+e@ JYmiaJ)f)J@|!$6%M}3:1XzW: AM~?J1t3)h&/oXN8,P O_]$.2Bmkw6 74 I^JPRnemB'Py`)JP~W["b&nqOzo[UrkFmAHHIqE9"ubY"a'b5/pvRe!p#6 ,,.,KR#.NXpF7uX;3VuKG}59:cI"WN<(8{ b+TmHF?}k"Qz7:`bs#-ne!fr6x,#^BVQ.Tl<-w:`l1<9Kwu.ZYG-wNsWY<"M"]Ko0+X8GsxI4)^YC_mH/"S(&?"T_flS7mPE/?-PSNkx8JqM]-b6Z2_Ge_jO!jX"Pa(ZhoicBv:wY:.A>0NbJ%h$wfLKCQp f" jz{]mD$IjFsz}F7_b_V}x*RW %ezdz31:P]|*Yf :`DS;im#^f ?2N8} 1D+!D4r9d sWh4tK=r#Y9 Qovnvd nrazH~ zej)"!1xoD%HwX{K`'-OE),WD&`n@4BKM.tIDv+?;l'F5+=l81$xa(5kuB/ E{r)leQ_iNVQ%Qj3c_~+JWH;Gpt;d$&$R,ptQ~b0p( {df> f 6&EizW5P"Anr"S MIrh3LE!FEc12NHgzi Y>cJ:m4U{:wW>W!kk-[a~>U]oo_I]ko8+6J+Q5t mQ!%)mjZEJ`|2L:Q''qUOrS^>>Z9++X*mcBU0(6 Qj*n}v>GKnv^~~OCOG-/~=?4= UMU[fcPng0of1~'P6v*SR ei,&Hv^`3Z y`-y{iPVTl?gd2 fL6CvOL@fo|Y80BgCVhk "?fK5I.qLD7!-$N'u'53'p]7D9- LJedRXs+p>6~A@ S7(bClU!X1z+h,D8E` Z*@gf]('{Lb}]qJgybf=.>}@"4@lo{ow>f= %1l>y<,;+ey}>+EX%'SVF+Wo-e]^kXiJ`BDT,e)U JWTe&&D]6[J94#/|Nt.$^,4D]vLR/hA]!>)n +93^OE+{=[tQ$3 u8O*"ZgW91EfrUPx +LK;V4yOxV#-;Q +r#rdPC?3E`L^e'Z{upifc;>`j/;geuogfKVfrv#PXnk9<>@F+~O{v}[[z:?ccz7I;.]nHYE; nck%46MH&!ji&q@@ Gky'2es9VZWr -r "VxI3sToS/S+Hd"-'dgOt6lDb>x~_G//bHGzR6V;mi8RNbK32^>Lu8w-Q>n-|~4Q8zz{3F.;4A02jq]nwCSQri-9Ce|f@R-C/7_8a?wUsj?wr-Ezf~v{2SRAK&:og_g{O->tvamV29o4<:JRm76bD^OpjJ=/'udcs*QhTYxz;TJ+~T!wO]EIti3QI|]cy`^)x7z1_=VmzyemJw?*ozq-vV(7S#_c%:N,O.v.>`bYY|eTg2_XpJ/|fXxWz^z7aj-o^ /Cx Zz>{v9Z)kjB=h zQ5XJEGgVJQWcU Ku^>OQ@X77mGSy3cKSp_,+jYnJV^5/,Yj*URwk65 Sh4@ k29I-9D"m;h()9GC'[r# T*kG)w}~I+33wyV63f/8+s1knQ_{.og= 6^WZt9_L'q.2FMw]nU/p;0Ac_;aVunIcLThu'o"}tw.;f]jawfO=g|X90rn7M}{-yw5s*j5W8ms 2wi{]5u@s ,t2^76 t^7nCoz0kgu7h@o8G ^9M+=J_=c2?)s|6-Euo._^AI,sLt_6D.|90i@8zw@uFcBioi1CyMczWdGN>Ki7[aX1atYVmF0fA5l1$_X"=H PN:|,{/-2Ha;_mk+O?gN,T:y}Rk>x?m"G I}u<:cD>gc`lKccUCk>~O/-JGz4b7>sL:'6mC} _(H^x_[;B_A(*-![Lep]"!]A<[ecF26q[a uO;XV rdv=W:;$NbPL:aG('V|$wb!M /.&ja%1e1H6@`2b1xAab^'e?#N}?'{D2BRJ :eE_YT l /m)>&le:i]@f |am2`aALmH w `,b6Ig 9cz7'k Wx:M?_)aFvlnlosnO?g">quS[ 2 &Ay(b2O 1lax!?Xq}1u~ aBA8u pymb]nFe^^r,#+z-xhy}{zc:|x%l6c1tyPTh !av/2$Y7^J;a8 /Kd4Pb!&=v, tKC=ebH~0:II'I3VEtJ87:~2}2o x>-C-ikWD5WmNlWC Cvw{xWdDkt%OLbHp*c[._5&t:)> _&|MEVR{dor^z+V@T3U$ZNi#P|?];}Dd`&:/,KgO8zl9Ds'Ai]=9C[=3HH&~1,67FDJ#g3#_wdz>=n/[^YS 6s..6u)Yq.(ar)X(w*n/~M?t~ei4+R@KKk^/xU+U+:w()Oby+n6zasA]b|rOtjKt}/5.tC%4_CeL};>?whZrhqCA$G;rPz(wZ3u@.r/PybbfhIW Vn@* =.(d/1(PO/nxhwyFy/h7SQ"UU7Wm2VZ)zvin>KG+O>F("(~@ffXku_0KJBYm-Efz{|c+{hqloM#+:MOyS $*b#}g FwLo|J7OjoX(@ 1*"eY^.@Zeg0fLt$HPvflA._D4b&zp8~f'f-8A>OR9,%_o}YbDz Akxjj H~);G/ 4Prnjfp?xoEp)l[L@c}74ztF`#V.iR4+RZN7 Ktvr]wy=5ZdbOonhF )av'f$L/LGr,PTcYE,d&W_LTh6FyRErl>?QJQg6k>vCSV*&Z:H^,2VyUUW?s'Rllr7UXR>9$mrpmu+@&Z#jM"c>,fA2~?T7:YBRDxA&{{wgU[J[lg &#!COA_G3L3 /PvfW2 0A}EM6&MJ~[ddk!XF6U X?~fy`'#iwi!L&/OZ^/6LO]aSrdLs"9y1.c^W*W+k6"x=g WGM`NkbK; 6hQ @W8^Fr3^/]n0~C;Ow'Ms'+b>Q'Ej#KIJs.|ArGMZEc4llR_{7,/?NJ 'EcXc &oruz|c`M@!=@czvB:|0`S*eHuA+ 7Ui 7&K}6=g~AY~jn?l` j[Zb7w$=PO>_p9_ }|kz^>^+E&JiUGD@h=7'@"e25AYYGeZ9)"IVY0lc#Hx?~Fzw>-~2a~*;C[s$pf FG^GV{{[jV#dVQfMEgwEQ7n[vP'XK#CcM%hL V$F*T;_D@+FAPrUr;NJN-=R"*P x(s!BEKB"5U`'%=E L*s,`&EZr1;y+0SZ*:yRT0eW}351 ff~kS&, b@>4x-n&Z{r9~?.Z6^~y(.hdAsQJkU2F4P[yzzG?*Ks>pQi>?3YXiUA #P G@:7G()|@]k|x(n)"~BbAI 5FNzxf}n<.m gbu="">l=wU_eLauh-@Yc* mXBn?/[SyQ'W}syvtQ-U6:+XKMQ)(4B48[yqLR~IE[uQk2ia_![2<_/>

Zc]>!we >'q6s>n@0aS~!I1Y6vV7J``4G$SGKjt?~ZEbvLWp"xETq [ ky/xH4iUB!X8L[q,5Z'cPL,>qKGV,cd72g]Xsn.Vh7%:6cwf,Y7njiF(E7: ssmY%XX.Ts>>v'p~@u]5b^; D(b{leDv M9:zT6R^3mk$^biv& \_%0L&.0Vd=Y,@=@=^vC!W!8Dy>E7_u_uAyy6xzGv[}{HkuTX$ I4nhlWtEt( Zhh]Ko8+[HS,NzHO INlnEI8EbH|C1MKoij[8iN]/]VMI~_pF8Y(nZhmp6R9/Kz^scV}tLj;3q/U="Ye?y%z%/yV)R*p7o[]ZU(YIohCiiwY6O2LAB]H+>o(4*d|+He_Wog6!Wu) mohEmB3NXlZI{J_E $xISAE/Rh43R$v!jmV R..k2naN4.b+zw6IrZ=HL.#>4K]RFxQ0|SPO#R.;'-T~w0/3i3+zJ/ls3}d<4V2{^{HO^F{mSvZN(A?tMpFuL}e-%rNy0X~!nIY6#^Z|l/%?nNphNzu0I /4%]Ko@+HJ%J>UzSO#I7`vJm!3qgg}Uwwk[Yx]eS_],J?F!>Pjh.Zv|qzj#%U-VZk0E5o^ksDc?5OF%fGT@bk5+6w.TsE78`-Mra&m`{aB$LJcsWejL{.-s* ROiNsZg_K`}>fXp/IP$+v%dJ+2n g:)1F8xf'7hE8, -F=yF :[LMDM.( 80O+|D3WBa" ) J6AL#ZP]T#K9$44W #^HjKz~`Ii]77-Ue>A~7^NAs}^lwD-lZfS-XU,SO'U+2>O7v6:4Z]u{5K;UzH; in+S9`x9N" u l`x4M]t 4jk}Oe5HY%LeDV-[#R{v[M]) jD% wQ0o-w(7e#6"^NX%8

See the original post here:
Hello, again, Dolly - The Economist

Science Daily

Your brain's got rhythm: Synthetic brain mimics Science Daily Salk scientists create synthetic brain systems called 'circuitoids' to better understand dysfunctional movements in Parkinson's, ALS and other diseases. Confocal microscope immunofluorescent image of a spinal cord neural circuit made entirely from stem ... and more »

Read the original here:
Your brain's got rhythm: Synthetic brain mimics - Science Daily

Back to Browse Journals Journal of Neurorestoratology Volume 5

Zhijian Cheng, Xijing He

Department of Orthopedics, The Second Affiliated Hospital of Xian Jiaotong University, Xian, Shaanxi, Peoples Republic of China

Abstract: Spinal cord injury (SCI) is a traumatic event that involves not just an acute physical injury but also inflammation-driven secondary injury. Macrophages play a very important role in secondary injury. The effects of macrophages on tissue damage and repair after SCI are related to macrophage polarization. Stem cell transplantation has been studied as a promising treatment for SCI. Recently, increasing evidence shows that stem cells, including mesenchymal stem, neural stem/progenitor, and embryonic stem cells, have an anti-inflammatory capacity and promote functional recovery after SCI by inducing macrophages M1/M2 phenotype transformation. In this review, we will discuss the role of stem cells on macrophage polarization and its role in stem cell-based therapies for SCI.

Keywords: stem cells, macrophages, spinal cord injury, polarization

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Original post:
Anti-inflammatory effect of stem cells against spinal cord injury via | JN - Dove Medical Press

Belleville News-Democrat

A baby's first act, saving a life Belleville News-Democrat Currently, stem cells are being researched to try to find cures or ways to treat autism, spinal cord injury, stroke recovery and Alzheimer's disease. Doll-Pollard said that it is incredibly important for the family to weigh these options before a ...

View post:
A baby's first act, saving a life - Belleville News-Democrat

February 15, 2017 A single human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM). Cells such as these were used to assess tyrosine kinase inhibitors for cardiotoxicity in a high-throughput fashion. Credit: Dr. Arun Sharma at Dr. Joseph Wus laboratory at Stanford University

Researchers at the Stanford University School of Medicine used heart muscle cells made from stem cells to rank commonly used chemotherapy drugs based on their likelihood of causing lasting heart damage in patients.

Drugs known as tyrosine kinase inhibitors can be an effective treatment for many types of cancers, but they also have severe and sometimes fatal side effects. Using lab-grown heart cells, Stanford researchers were able to assess the drugs' various effects on heart muscle cells, including whether the cells survived, were able to beat rhythmically and effectively, responded appropriately to electrophysiological signals and communicated with one another.

The researchers found that their assay can accurately identify those tyrosine kinase inhibitors already known to be the most dangerous in patients. In the future, they believe their system may prove useful in the early stages of drug development to screen new compounds for cardiotoxicity.

"This type of study represents a critical step forward from the usual process running from initial drug discovery and clinical trials in human patients," said Joseph Wu, MD, PhD, director of the Stanford Cardiovascular Institute and a professor of cardiovascular medicine and of radiology. "It will help pharmaceutical companies better focus their efforts on developing safer drugs, and it will provide patients more effective drugs with fewer side effects."

A paper describing the research will be published Feb. 15 in Science Translational Medicine. Wu, who holds the Simon H. Stertzer Professorship, is the senior author. Former graduate student Arun Sharma, PhD, is the lead author.

'Multiple measurements'

"We used multiple measurements to accurately predict which of the tyrosine kinase inhibitors were the most cardiotoxic," said Sharma. "The drugs with the lowest safety indices in our study were also those identified by the Food and Drug Administration as the most cardiotoxic to patients. Other drugs that are not as cardiotoxic performed much better in our assays."

Validating the researchers' cardiac-safety test on drugs with extensive clinical track records is necessary before the assay can be used to predict with confidence the likely clinical outcomes of drugs still under development.

The video will load shortly

Sharma, Wu and their colleagues created heart muscle cells called cardiomyocytes from induced pluripotent stem cells, or iPS cells, from 11 healthy people and two people with kidney cancer. They grew the lab-made cardiomyocytes in a dish and tested the effects of 21 commonly used tyrosine kinase inhibitors on the cells.

They found that treatment with drug levels equivalent to those taken by patients often caused the cells to beat irregularly and begin to die. The cells also displayed differences in the electrophysiological signaling that controls their contraction. The researchers used these and other measurements to develop a cardiac safety index for each drug.

They found that those drugs known to be particularly dangerous to heart function, such as nilotinib, which is approved for the treatment of chronic myelogenous leukemia, and vandetanib, which is approved for the treatment of some types of thyroid cancer, also had the lowest safety indices based on the assay; conversely, those known to be better tolerated by patients ranked higher on their safety index. Prescribing information for both nilotinib and vandetanib contains warnings from the FDA about the drugs' potential cardiotoxicity.

An activity increase in an insulin responsive pathway

Six of the 21 tyrosine kinase inhibitors tested were assigned cardiac safety indices at or below 0.1the threshold limit at which the researchers designated a drug highly cardiotoxic. Three of these six are known to inhibit the same two signaling pathways: VEGFR2 and PDGFR. The researchers noticed that cells treated with these three drugs ramped up the activity of a cellular signaling pathway that responds to insulin or IGF1, an insulinlike growth factor.

This discovery, coupled with the fact that treatment with insulin or IGF1 is known to enhance heart function during adverse cardiac events such as heart attacks, led the researchers to experiment further. They found that exposing the cells to insulin or IGF1 made it less likely they would die due to tyrosine kinase inhibitors blocking the VEGFR2 and PDGFR pathways. Although more research is needed, these findings suggest it may be possible to alleviate some of the heart damage in patients receiving these chemotherapies.

The current study mirrors another by Wu's lab that was published in April 2016 in Nature Medicine. That research focused on the toxic effect of a chemotherapy drug called doxorubicin on iPS cell-derived cardiomyocytes. Doxorubicin, which indiscriminately kills any replicating cells, is increasingly being replaced by more targeted, cancer-specific therapies such as the tyrosine kinase inhibitors tested in the current study.

"The switch from doxorubicin is a result of the paradigm shift in cancer treatment to personalized, precise treatment as emphasized by President Obama's 2015 Precision Medicine Initiative," said Wu. "Moving even further, we're discovering that many tyrosine kinase inhibitors are themselves significantly cardiotoxic, and some have been withdrawn from the market. There is a critical need for a way to 'safety test' all drugs earlier in development before they are administered to patients. Our drug safety index is a step in that direction."

Explore further: Stem cell-based screening methods may predict heart-related side effects of drugs

More information: "High-throughput screening of tyrosine kinase inhibitor cardiotoxicity with human induced pluripotent stem cells," Science Translational Medicine, stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aaf2584

Coaxing stem cells from patients to become heart cells may help clinicians personalize drug treatments and prevent heart-related toxicity.

Heart muscle cells made from induced pluripotent stem cells faithfully mirror the expression patterns of key genes in the donor's native heart tissue, according to researchers at the Stanford University School of Medicine. ...

Researchers at Moffitt Cancer Center have determined that chronic myeloid leukemia patients who are treated with a class of oral chemotherapy drugs known as a tyrosine kinase inhibitors have significant side effects and quality-of-life ...

Some cancers can be effectively treated with drugs inhibiting proteins known as receptor tyrosine kinases, but not those cancers caused by mutations in the KRAS gene. A team of researchers led by Jeffrey Engelman, at Massachusetts ...

Acute myeloid leukemia (AML) is a cancer of myeloid stem cells that develops in both adult and pediatric populations. Mutations that cause hyperactivation of the FMS-like tyrosine kinase 3 (FLT3) are commonly found in AML, ...

Fat cells are not simply big blobs of lipid quietly standingby in the bodyinstead, they send out hormones and other signaling proteins that affect many types of tissues. Scientists at Joslin Diabetes Center now have identified ...

Researchers at the Stanford University School of Medicine used heart muscle cells made from stem cells to rank commonly used chemotherapy drugs based on their likelihood of causing lasting heart damage in patients.

Research published today in Nature from scientists at Huntsman Cancer Institute (HCI) at the University of Utah shows how epithelial cells naturally turn over, maintaining constant numbers between cell division and cell death.

Scientists are working to understand the mechanisms that make weight loss so complicated. Exercise burns calories, of course, but scientists are also looking at how the body burns more energy to stay warm in cold temperatures.

Biologists have known for decades that enduring a short period of mild stress makes simple organisms and human cells better able to survive additional stress later in life. Now, scientists at Sanford Burnham Prebys Medical ...

A puzzling question has lurked behind SMA (spinal muscular atrophy), the leading genetic cause of death in infants.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Read the original post:
Scientists create scorecard index for heart-damaging chemo drugs - Medical Xpress

Seventy-year-old Peggy Agar has known since she was in her 40s that she and her 12 siblings might be at risk for familial cardiomyopathy, a genetic form of heart disease.

Her mother was diagnosed with it in 1987, and several of her brothers were also subsequently diagnosed with cardiomyopathy.

Given our family history, our family knew we had to be vigilant to keep our hearts as strong as possible, says Agar, who lives in Bloomfield.

But now thanks to the power of genetic testing at UConn Healths Pat and Jim Calhoun Cardiology Center, Agar and her family can determine which family members may be at risk.

Through a routine blood sample, Agars gene sequences were analyzed by Dr. Travis Hinson, a cardiovascular physician-scientist who is a new faculty member with a joint appointment at UConn Health and the Jackson Laboratory for Genomic Medicine.

Hinsons advanced genetic analysis revealed that Agar carries a gene mutation that causes dilated cardiomyopathy, a disease of the heart muscle that potentially leads to an enlarged, weakened heart and ultimately heart failure. He identified that Agar carries a mutation in the largest gene in the body called titin that leads to dilated cardiomyopathy in about 1 in 5 patients with a positive family history. In 2015, his laboratory published these findings in the journal Science, where he studied miniature beating human heart tissues engineered from stem cells from patients with conditions similar to Agars.

Hinson says knowing their genetic predisposition allows patients and families to understand why heart disease may continue to be prevalent generation after generation in their family.

If you carry the cardiomyopathy gene, you have a 50 percent chance of passing it to your offspring, says Hinson. Now with the power of genetic testing, we can tell each family member definitely early in their life whether they carry the cardiomyopathy genetic mutation, and intervene early to try to prevent any symptoms of the disease before they occur.

Agar says the genetic test results will arm her familys younger and future generations with important knowledge.

Now our family can better safeguard ourselves and younger generations at an early age to take extra precautions when it comes to our heart health, she says. Because of the way this myopathy develops in our family, we have learned that it is very important when we seek medical care that the physicians we see are aware of this family history.

Another positive aspect of the testing is that family members who are found not to have the gene no longer need to worry about passing the gene on to their children.

Agar has received comprehensive treatment from a team of physicians at UConn Healths Calhoun Cardiology Center, including cardiologist Dr. Jason Ryan and electrophysiologist Dr. Christopher Pickett. Since she was first diagnosed with cardiomyopathy in 2009, she has been treated for its complications. These include atrial fibrillation, the most common form of arrhythmia, and ventricular tachycardia, life-threatening and chaotic heart beats that can cause premature or sudden death. To protect her heart against dangerous arrhythmias, Agar takes daily medication; has received cardioversions (which convert an arrhythmia to a normal rhythm) and an ablation procedure (the destruction of tinyparts of heart tissue with radio frequency waves that are triggering arrhythmia); and has an implantable cardio-defibrillator.

As a result of the personalized team approach among the cardiologists who care for her at the Calhoun Cardiology Center, Agars heart function has been nearly normalized. She is grateful to the entire team.

Ive been fortunate, she says. UConns cardiac health team and their staff have been very supportive. They are truly experts in their field and treat me in a very professional and personal manner. They welcome questions and listen to my concerns. They convey the feeling that they truly care about my well-being.

Cardiomyopathy is the most common cause of heart failure. While it can be a genetic condition, it can also be caused by a heart attack or unhealthy lifestyle.

Agar advises others who may have a recurring theme of heart trouble in their family to seek care and not ignore it. With appropriate treatment, she says, cardiac problems dont necessarily have to significantly impact your quality of life. Remember that you are in charge of your own health. Pay attention to the advice of your health care professionals and do those things that are necessary for good health.

To learn more about the Calhoun Cardiology Center at UConn Health, visit: health.uconn.edu/cardiology.

Read the rest here:
Cardiovascular Genetic Testing Empowers Patient, Family - UConn Today

Wyoming resident and pediatric nurse Elizabeth Groter has partnered with DKMS (Dynamic Kernel Module Support), the nonprofit leading the fight against blood cancer, to host a bone marrow registration drive in Toulon Friday. The event will be held from 3 to 7 p.m. at the Stark County High School cafeteria, and will help register potential lifesaving donors. Anyone in good general health who is between 18 and 55 can register. The process involves filling out a simple form, understanding the donation methods and swabbing the inside of each cheek for 30 seconds. There is no charge to register. Donations help DKMS cover the $65 registration processing fee but are not required. Groter is a pediatric nurse at Childrens Hospital of Illinois, and a DKMS representative. She was inspired to host a drive with DKMS after experiencing first-hand how simple it is to be added to the KDMS bone marrow registry. With her job experience, Groter has met countless children battling leukemia and other blood cancers who are in need of bone marrow transplants, and wanted to make a difference by helping to grow the registry to find lifesaving matches for patients. Groters uncle is a leukemia survivor and another source of her inspiration. Becoming a part of the bone marrow registry to be a possible match for someone with blood cancer is so incredibly easy, and Im going to make it even easier for you. By doing something as simple as this, you could possibly change someones life in an instant, said Groter. According to DKMS, 70 percent of people suffering from blood-related illnesses must rely on donors outside their families to save their life. Swabbing your cheek is all it takes to register as a potential donor. Anyone who wishes to register as a potential donor but is unable to attend Fridays drive can register online at http://www.dkms.org. DKMS is an international nonprofit organization dedicated to eradicating blood cancers like leukemia and other blood-related illnesses. The organization inspires men and woman around to the world to register as bone marrow and blood stem cell donors.

Original post:
Nurse asking people to sign up as bone-marrow donors - Kewanee Star Courier

Human stem cells grown on Kyoto University's "fiber-on-fiber" culturing system(Credit: Kyoto University)

Mighty promising as they are, stem cells certainly aren't easy to come by. Recent scientific advances have however given their production a much-needed boost, with a Nobel-prize winning technology that turns skin cells into embryonic-like stem cells and another that promises salamander-like regenerative abilities being just a couple of examples. The latest breakthrough in the area comes from Japanese researchers who have developed a nanofiber matrix for culturing human stem cells, that they claim improves on current techniques.

The work focuses on human pluripotent stem cells (hPSCs), which have the ability to mature into any type of adult cell, be they those of the eyes, lungs or hair follicles. But that's assuming they can be taken up successfully by the host. Working to improve the odds on this front, scientists have been exploring ways of culturing pluripotent stem cells in a way that mimics the physiological conditions of the human body, allowing them to grow in three dimensions rather than in two dimensions, as they would in a petrie dish.

Among this group is a team from Japan's Kyoto University, which has developed a 3D culturing system it says outperforms the current technologies that can only produce low quantities of low-quality stem cells. The system consists of gelatin nanofibers on a synthetic mesh made from biodegradable polyglycolic acid, resulting in what the researchers describe as a "fiber-on-fiber" (FF) matrix.

The team found that seeding human embryonic stem cells onto this type of matrix saw them adhere well, and enabled an easy exchange of growth factors and supplements. This led to what the researchers describe as robust growth, with more than 95 percent of the cells growing and forming colonies after just four days of culture.

And by designing a special gas-permeable cell culture bag, the team also demonstrated how they could scale up the approach. This is because several of the cell-loaded matrices can be folded up and placed inside the bag, with testing showing that this approach yielded larger again numbers of cells. What's more, the FF matrix could even prove useful in culturing other cell types.

"Our method offers an efficient way to expand hPSCs of high quality within a shorter term," the team writes in its research paper. "Additionally, as nanofiber matrices are advantageous for culturing other adherent cells, including hPSC-derived differentiated cells, FF matrix might be applicable to the large-scale production of differentiated functional cells for various applications."

The research was published in the journal Biomaterials.

See the original post:
Nanofiber matrix sends stem cells sprawling in all directions - Gizmag - New Atlas

While a number of companies have dabbled in this space, the following players are facilitating the development of iPS cell therapies: Cellular Dynamics International (CDI),Cynata Therapeutics, RIKEN, and Astellas (previously Ocata Therapeutics).

While each iPS cell therapy group is considered in detail below, Cellular Dynamics International (CDI) is featured first, because it dominates the iPSC industry. CDI also recently split into two business units, a Life Science Unit and a Therapeutics Unit, demonstrating a commercial strategy for its iPS cell therapy development.

Founded in 2004 and listed on NASDAQ in July 2013, Cellular Dynamics International (CDI) is headquartered in Madison, Wisconsin. The company is known for itsextremely robust patent portfolio containing more than 900 patents.

According to the company, CDI is the worlds largest producer of fully functional human cells derived from induced pluripotent stem (iPS) cells.[1] Their trademarked, iCell Cardiomyocytes, derived from iPSCs, are human cardiac cells used to aid drug discovery, improve the predictability of a drugs worth, and screen for toxicity. In addition, CDI provides: iCell Endothelial Cells for use in vascular-targeted drug discovery and tissue regeneration, iCell Hepatocytes, and iCell Neurons for pre-clinical drug discovery, toxicity testing, disease prediction, and cellular research.[2]

Induced pluripotent stem cells were first produced in 2006 from mouse cells and in 2007 from human cells, by Shinya Yamanaka at Kyoto University,[3] who also won the Nobel Prize in Medicine or Physiology for his work on iPSCs.[4] Yamanaka has ties toCellular Dynamics International as a member of the scientific advisory board of iPS Academia Japan. IPS Academia Japan was originally established to manage the patents and technology of Yamanakas work, and is now the distributor of several of Cellular Dynamics products, including iCell Neurons, iCell Cardiomyocytes, and iCell Endothelial Cells.[5]

Importantly, in 2010 Cellular Dynamics became the first foreign company to be granted rights to use Yamanakas iPSC patent portfolio.Not only has CDI licensed rights to Yamanakas patents, but it also has a license to use Otsu, Japan-based Takara Bios RetroNectin product, which it uses as a tool to produce its iCell and MyCell products.[6]

Furthermore, in February 2015, Cellular Dynamics International announcedit would be manufacturing cGMP HLA Superdonor stem cell lines that will support cellular therapy applications through genetic matching.[8] Currently, CDI has two HLA superdonor cell lines that provide a partial HLA match to approximately 19% of the population within the U.S., and it aims to expand its master stem cell bank by collecting more donor cell lines that will cover 95% of the U.S. population.[9]The HLA superdonor cell lines were manufactured using blood samples, and used to produce pluripotent iPSC lines, giving the cells the capacity to differentiate into nearly any cell within the human body.

On March 30, 2015, Fujifilm Holdings Corporation announced that it was acquiring CDI for $307 million, allowingCDI tocontinue to run its operations in Madison, Wisconsin, and Novato, California as a consolidated subsidiary of Fujifilm.[14] A key benefit of the merger is that CDIs technology platform enables the production of high-quality fully functioning iPSCs (and other human cells) on an industrial scale, while Fujifilm has developed highly-biocompatible recombinant peptidesthat can be shaped into a variety of forms for use as a cellular scaffoldin regenerative medicinewhen used in conjunction with CDIs products.[15]

Additionally, Fujifilm has been strengthening its presence in the regenerative medicine field over the past several years, including a recent A$4M equity stake in Cynata Therapeutics and anacquisition ofJapan Tissue Engineering Co. Ltd.in December 2014. Most commonly called J-TEC, Japan Tissue Engineering Co. Ltd. successfully launched the first two regenerative medicine products in the country of Japan.According toKaz Hirao, CEO of CDI, It is very important for CDI to get into the area of therapeutic products, and we can accelerate this by aligning it with strategic and technical resources present within J-TEC.

Kaz Hirao also states,For our Therapeutic businesses, we will aim to file investigational new drugs (INDs) with the U.S. FDA for the off-the-shelf iPSC-derived allogeneic therapeutic products. Currently, we are focusing on retinal diseases, heart disorders, Parkinsons disease, and cancers. For those four indicated areas, we would like to file several INDs within the next five years.

Finally, in September 2015, CDI againstrengthened its iPS cell therapycapacity by setting up a new venture, Opsis Therapeutics. Opsis is focused on discovering and developing novel medicines to treat retinal diseases and is apartnership with Dr. David Gamm, the pioneer of iPS cell-derived retinal differentiation and transplantation.

In summary, several key events indicate CDIs commitment to developing iPS cell therapeutics, including:

Australian stem cell company Cynata Therapeutics (ASX:CYP) is taking a unique approachby creating allogeneic iPSC derived mesenchyal stem cell (MSCs)on a commercial scale.Cynatas Cymerus technology utilizes iPSCs provided by Cellular Dynamics International, a Fujifilm company, as the starting material for generating mesenchymoangioblasts (MCAs), and subsequently, for manufacturing clinical-gradeMSCs.According to Cynatas Executive Chairman Stewart Washer who was interviewed by The Life Sciences Report, The Cymerus technology gets around the loss of potency with the unlimited iPS cellor induced pluripotent stem cellwhich is basically immortal.

OnJanuary 19, 2017, Fujifilm took anA$3.97 million (10%) strategic equity stakein Cynata, positioning the parties to collaborate on the further development and commercialisation of Cynatas lead Cymerus therapeutic MSC product CYP-001 for graft-versus-host disease (GvHD). (CYP-001 is the product designation unique to the GVHD indication). The Fujifilm partnership also includes potential future upfront and milestone payments in excess of A$60 million and double-digit royalties on CYP-001 product net sales for Cynata Therapeutics, as well as strategic relationship for potential future manufacture of CYP-001 and certain rights to other Cynata technology.

One of the key inventors of Cynatas technology is Igor Slukvin, MD, Ph.D., Scientific Founder of Cellular Dynamics International (CDI) and Cynata Therapeutics. Dr. Slukvin has released more than 70 publications about stem cell topics, including the landmark article in Cell describing the now patented Cymerus technique. Dr. Slukvins co-inventor is Dr. James Thomson, the first person to isolate an embryonic stem cell (ESC) and one of the first people to create a human induced pluripotent stem cell (hiPSC). Dr. James Thompson was theFounder of CDI in 2004.

There are three strategic connections between Cellular Dynamics International (CDI) and Cynata Therapeutics, which include:

Recently, Cynata received advice from the UK Medicines and Healthcare products Regulatory Agency (MHRA) that its Phase I clinical trial application has been approved, titledAn Open-Label Phase 1 Study to Investigate the Safety and Efficacy of CYP-001 for the Treatment of Adults With Steroid-Resistant Acute Graft Versus Host Disease. It will be the worlds first clinical trial involving a therapeutic product derived from allogeneic (unrelated to the patient) induced pluripotent stem cells (iPSCs).

Participants for Cynatas upcoming Phase I clinical trial will be adults who have undergone an allogeneic haematopoietic stem cell transplant (HSCT) to treat a haematological disorder and subsequently been diagnosed with steroid-resistant Grade II-IV GvHD.The primary objective of the trial is to assess safety and tolerability, while the secondary objective is to evaluate the efficacy of two infusions of CYP-001 in adults with steroid-resistant GvHD.

Using Professor Yamankas Nobel Prize winning achievement of ethically uncontentious iPSCs and CDIs high quality iPSCs as source material, Cynata has achieved two world firsts:

Cynata has also released promising pre-clinical data in Asthma, Myocardial Infarction (Heart Attack), andCritical Limb Ischemia.

There are four key advantages of Cynatas proprietary Cymerus MSC manufacturing platform.Because the proprietary Cymerus technology allows nearly unlimited production of MSCs from a single iPSC donor, there is batch-to-batch uniformity. Utilizing a consistent starting material allows for a standardized cell manufacturing process and a consistent cell therapy product. Unlike other companies involved with MSC manufacturing, Cynata does not require a constant stream of new donors in order to source fresh stem cells for its cell manufacturing process, nor does it require the massive expansion of MSCs necessitated by reliance on freshly isolated donations.

Finally, Cynata has achieved a cost-savings advantage through its uniqueapproach to MSCmanufacturing. Its proprietary Cymerus technology addresses a critical shortcoming in existing methods of production of MSCs for therapeutic use, which is the ability to achieve economic manufacture at commercial scale.

On June 22, 2016, RIKEN announced that it is resuming its retinal induced pluripotent stem cell (iPSC) study in partnership with Kyoto University.

2013 was the first time in which clinical research involving transplant of iPSCs into humans was initiated, led by Masayo Takahashi of the RIKEN Center for Developmental Biology (CDB)in Kobe, Japan. Dr. Takahashi and her team wereinvestigating the safety of iPSC-derived cell sheets in patients with wet-type age-related macular degeneration. Althoughthe trial was initiated in 2013 and production of iPSCs from patients began at that time, it was not until August of 2014 that the first patient, a Japanese woman, was implanted with retinal tissue generated using iPSCs derived from her own skin cells.

A team of three eye specialists, led by Yasuo Kurimoto of the Kobe City Medical Center General Hospital, implanted a 1.3 by 3.0mm sheet of iPSC-derived retinal pigment epithelium cells into the patients retina.[196]Unfortunately, the study was suspended in 2015 due to safety concerns. As the lab prepared to treat the second trial participant, Yamanakas team identified two small genetic changes in the patients iPSCs and the retinal pigment epithelium (RPE) cells derived from them. Therefore, it is major news that theRIKEN Institute will now be resuming the worlds first clinical study involving the use of iPSC-derived cells in humans.

According to the Japan Times, this attempt at the clinical studywill involve allogeneic rather than autologous iPSC-derived cells for purposes of cost and time efficiency.Specifically,the researchers will be developing retinal tissues from iPS cells supplied by Kyoto Universitys Center for iPS Cell Research and Application, an institution headed by Nobel prize winner Shinya Yamanaka. To learn about this announcement, view this article fromAsahi Shimbun, aTokyo- based newspaper.

In November 2015 Astellas Pharma announced it was acquiring Ocata Therapeutics for $379M. Ocata Therapeutics is a biotechnology company that specializes in the development of cellular therapies, using both adult and human embryonic stem cells to develop patient-specific therapies. The companys main laboratory and GMP facility is in Marlborough, Massachusetts, and its corporate offices are in Santa Monica, California.

When a number of private companies began to explore the possibility of using artificially re-manufactured iPSCs for therapeutic purposes, one such company that was ready to capitalize on the breakthrough technology was Ocata Therapeutics, at the time called Advanced Cell Technology. In 2010, the company announced that it had discovered several problematic issues while conducting experiments for the purpose of applying for U.S. Food and Drug Administration approval to use iPSCs in therapeutic applications. Concerns such as premature cell death, mutation into cancer cells, and low proliferation rates were some of the problems that surfaced. [17]

As a result, the company shifted its induced pluripotent stem cell approach to producingiPS cell-derived human platelets, as one of the benefits of a platelet-based product is that platelets do not contain nuclei, and therefore, cannot divide or carry genetic information. While the companys Induced Pluripotent Stem Cell-Derived Human Platelet Program received a great deal of media coverage in late 2012, including being awarded the December 2012 honor of being named one of the 10 Ideas that Will Shape the Yearby New Scientist Magazine,[178] unfortunately the company did not succeed in moving the concept through to clinical testing in 2013.

Nonetheless, Astellas is clearly continuing to develop Ocatas pluripotent stem cell technologies involving embryonic stem cells (ESCs) and induced pluripotent stem cells (iPS cells). In a November 2015 presentation by Astellas President and CEO, Yoshihiko Hatanaka, he indicated that the company will aim to develop an Ophthalmic Disease Cell Therapy Franchise based around its embryonic stem cell (ESC) and induced pluripotent stem cell (iPS cell) technology. [19]

Footnotes [1] CellularDynamics.com (2014). About CDI. Available at: http://www.cellulardynamics.com/about/index.html. Web. 1 Apr. 2015. [2] Ibid. [3] Takahashi K, Yamanaka S (August 2006).Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.Cell126(4): 66376. [4] 2012 Nobel Prize in Physiology or Medicine Press Release. Nobelprize.org. Nobel Media AB 2013. Web. 7 Feb 2014. Available at: http://www.nobelprize.org/nobel_prizes/medicine/laureates/2012/press.html. Web. 1 Apr. 2015. [5] Striklin, D (Jan 13, 2014). Three Companies Banking on Regenerative Medicine. Wall Street Cheat Sheet. Retrieved Feb 1, 2014 from, http://wallstcheatsheet.com/stocks/3-companies-banking-on-regenerative-medicine.html/?a=viewall. [6] Striklin, D (2014). Three Companies Banking on Regenerative Medicine. Wall Street Cheat Sheet [Online]. Available at: http://wallstcheatsheet.com/stocks/3-companies-banking-on-regenerative-medicine.html/?a=viewall. Web. 1 Apr. 2015. [7] Cellular Dynamics International (July 30, 2013). Cellular Dynamics International Announces Closing of Initial Public Offering [Press Release]. Retrieved from http://www.cellulardynamics.com/news/pr/2013_07_30.html. [8] Investors.cellulardynamics.com,. Cellular Dynamics Manufactures Cgmp HLA Superdonor Stem Cell Lines To Enable Cell Therapy With Genetic Matching (NASDAQ:ICEL). N.p., 2015. Web. 7 Mar. 2015. [9] Ibid. [10] Cellulardynamics.com,. Cellular Dynamics | Mycell Products. N.p., 2015. Web. 7 Mar. 2015. [11]Sirenko, O. et al. Multiparameter In Vitro Assessment Of Compound Effects On Cardiomyocyte Physiology Using Ipsc Cells.Journal of Biomolecular Screening18.1 (2012): 39-53. Web. 7 Mar. 2015. [12] Sciencedirect.com,. Prevention Of -Amyloid Induced Toxicity In Human Ips Cell-Derived Neurons By Inhibition Of Cyclin-Dependent Kinases And Associated Cell Cycle Events. N.p., 2015. Web. 7 Mar. 2015. [13] Sciencedirect.com,. HER2-Targeted Liposomal Doxorubicin Displays Enhanced Anti-Tumorigenic Effects Without Associated Cardiotoxicity. N.p., 2015. Web. 7 Mar. 2015. [14] Cellular Dynamics International, Inc. Fujifilm Holdings To Acquire Cellular Dynamics International, Inc.. GlobeNewswire News Room. N.p., 2015. Web. 7 Apr. 2015. [15] Ibid. [16]Cyranoski, David. Japanese Woman Is First Recipient Of Next-Generation Stem Cells. Nature (2014): n. pag. Web. 6 Mar. 2015. [17] Advanced Cell Technologies (Feb 11, 2011). Advanced Cell and Colleagues Report Therapeutic Cells Derived From iPS Cells Display Early Aging [Press Release]. Available at: http://www.advancedcell.com/news-and-media/press-releases/advanced-cell-and-colleagues-report-therapeutic-cells-derived-from-ips-cells-display-early-aging/. [18] Advanced Cell Technology (Dec 20, 2012). New Scientist Magazine Selects ACTs Induced Pluripotent Stem (iPS) Cell-Derived Human Platelet Program As One of 10 Ideas That Will Shape The Year [Press Release]. Available at: http://articles.latimes.com/2009/mar/06/science/sci-stemcell6. Web. 9 Apr. 2015. [19] Astellas Pharma (2015). Acquisition of Ocata Therapeutics New Step Forward in Ophthalmology with Cell Therapy Approach. Available at: https://www.astellas.com/en/corporate/news/pdf/151110_2_Eg.pdf. Web. 29 Jan. 2017.

Read the original post:
Market Players Developing iPS Cell Therapies

February 14, 2017 Salk scientists create synthetic brain systems called 'circuitoids' to better understand dysfunctional movements in Parkinson's, ALS and other diseases. Confocal microscope immunofluorescent image of a spinal cord neural circuit made entirely from stem cells and termed a 'circuitoid.' Credit: Salk Institute

Not everyone is Fred Astaire or Michael Jackson, but even those of us who seem to have two left feet have got rhythmin our brains. From breathing to walking to chewing, our days are filled with repetitive actions that depend on the rhythmic firing of neurons. Yet the neural circuitry underpinning such seemingly ordinary behaviors is not fully understood, even though better insights could lead to new therapies for disorders such as Parkinson's disease, ALS and autism.

Recently, neuroscientists at the Salk Institute used stem cells to generate diverse networks of self-contained spinal cord systems in a dish, dubbed circuitoids, to study this rhythmic pattern in neurons. The work, which appears online in the February 14, 2017, issue of eLife, reveals that some of the circuitoidswith no external promptingexhibited spontaneous, coordinated rhythmic activity of the kind known to drive repetitive movements.

"It's still very difficult to contemplate how large groups of neurons with literally billions if not trillions of connections take information and process it," says the work's senior author, Salk Professor Samuel Pfaff, who is also a Howard Hughes Medical Institute investigator and holds the Benjamin H. Lewis Chair. "But we think that developing this kind of simple circuitry in a dish will allow us to extract some of the principles of how real brain circuits operate. With that basic information maybe we can begin to understand how things go awry in disease."

Nerve cells in your brain and spinal cord connect to one another much like electronic circuits. And just as electronic circuits consist of many components, the nervous system contains a dizzying array of neurons, often resulting in networks with many hundreds of thousands of cells. To model these complex neural circuits, the Pfaff lab prompted embryonic stem cells from mice to grow into clusters of spinal cord neurons, which they named circuitoids. Each circuitoid typically contained 50,000 cells in clumps just large enough to see with the naked eye, and with different ratios of neuronal subtypes.

With molecular tools, the researchers tagged four key subtypes of both excitatory (promoting an electrical signal) and inhibitory (stopping an electrical signal) neurons vital to movement, called V1, V2a, V3 and motor neurons. Observing the cells in the circuitoids in real time using high-tech microscopy, the team discovered that circuitoids composed only of V2a or V3 excitatory neurons or excitatory motor neurons (which control muscles) spontaneously fired rhythmically, but that circuitoids comprising only inhibitory neurons did not. Interestingly, adding inhibitory neurons to V3 excitatory circuitoids sped up the firing rate, while adding them to motor circuitoids caused the neurons to form sub-networks, smaller independent circuits of neural activity within a circuitoid.

"These results suggest that varying the ratios of excitatory to inhibitory neurons within networks may be a way that real brains create complex but flexible circuits to govern rhythmic activity," says Pfaff. "Circuitoids can reveal the foundation for complex neural controls that lead to much more elaborate types of behaviors as we move through our world in a seamless kind of way."

Because these circuitoids contain neurons that are actively functioning as an interconnected network to produce patterned firing, Pfaff believes that they will more closely model a normal aspect of the brain than other kinds of cell culture systems. Aside from more accurately studying disease processes that affect circuitry, the new technique also suggests a mechanism by which dysfunctional brain activity could be treated by altering the ratios of cell types in circuits.

Explore further: Scientists discover new mechanism of how brain networks form

More information: Matthew J Sternfeld et al, Speed and segmentation control mechanisms characterized in rhythmically-active circuits created from spinal neurons produced from genetically-tagged embryonic stem cells, eLife (2017). DOI: 10.7554/eLife.21540

Journal reference: eLife

Provided by: Salk Institute

Scientists have discovered that networks of inhibitory brain cells or neurons develop through a mechanism opposite to the one followed by excitatory networks. Excitatory neurons sculpt and refine maps of the external world ...

A new study presented in the journal Nature could change the view of the role of motor neurons. Motor neurons, which extend from the spinal cord to muscles and other organs, have always been considered passive recipients ...

When you're taking a walk around the block, your body is mostly on autopilotyou don't have to consciously think about alternating which leg you step with or which muscles it takes to lift a foot and put it back down. That's ...

We humans walk with our feet. This is true, but not entirely. Walking, as part of locomotion, is a coordinated whole-body movement that involves both the arms and legs. Researchers at the Biozentrum of the University of Basel ...

Dr. Kevin Collins carefully places a petri dish with what looks like a blotch of yellowish slime under a microscope. Magnified, the slime comes alive as hundreds of translucent worms, known as Caenorhabditis elegans, slither ...

Imagine yourself sitting in a noisy caf trying to read. To focus on the book at hand, you need to ignore the surrounding chatter and clattering of cups, with your brain filtering out the irrelevant stimuli coming through ...

Not everyone is Fred Astaire or Michael Jackson, but even those of us who seem to have two left feet have got rhythmin our brains. From breathing to walking to chewing, our days are filled with repetitive actions that ...

Whether we're navigating a route to work or browsing produce at the grocery store, our brains are constantly making decisions about movement: Should I cross the street now or at the intersection? Should I reach for the red ...

Pain is a signal of actual or potential damage to the body, so it is natural to think of it as a localized sensation: knee pain in the knee, back pain in the back and so on.

Researchers from the University of Toronto, Canada, have discovered a reason why we often struggle to remember the smaller details of past experiences.

The feel-good brain chemical dopamine appears to play a role in the development of a healthy bond between a mother and baby, a new study suggests.

Proteins are the building blocks of all cells. They are made from messenger RNA (mRNA) molecules, which are copied from DNA in the nuclei of cells. All cells, including brain cells regulate the amount and kind of proteins ...

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

See original here:
Your brain's got rhythm - Medical Xpress

Submit the press release

Transparency Market Research, in a report titled Stem Cells Market Global Industry Analysis, Size, Share, Growth, Trends and Forecast, 2012 2018, states that the global stem cells market is projected to witness remarkable growth from 2012 to 2018, fueled by increasing government support, unmet medical needs, rising stem cell banking services, and growing medical tourism. Driven by these factors, the global stem cells market is anticipated to expand at a 24.20% CAGR during the forecast period, rising from a value of US$26.2 bn in 2013 to US$119.5 bn by 2018.

Browse the full Stem Cells Market (Adult, Human Embryonic , Induced Pluripotent, Rat-Neural, Umbilical Cord, Cell Production, Cell Acquisition, Expansion, Sub-Culture) Global Industry Analysis, Size, Share, Growth, Trends and Forecast, 2012 2018 report at http://www.transparencymarketresearch.com/stem-cells-market.html

Rise in disposable income in emerging economies, the increasing prevalence of neurodegenerative disorders, development of the contract research industry, and replacement of animal tissue in drug discovery are also anticipated to contribute towards the overall growth of the stem cells market.By product, the stem cells market is categorized into adult stem cells, induced pluripotent stem cells, very small embryonic-like stem cells, human embryonic stem cells, and rat neural stem cells. Adult stem cells, which dominated the overall market in 2011, include mesenchymal stem cells, dental stem cells, neuronal stem cells, hematopoietic stem cells, and umbilical cord stem cells.

On the basis of technology, the stem cells market is segmented into stem cell acquisition, production, cryopreservation, and expansion and sub-culture. Stem cell acquisition is the largest as well as the most rapidly developing technological segment and includes bone marrow harvesting, umbilical cord blood, and apheresis. The segment of stem cell production includes cloning, isolation, in-vitro fertilization, and cell culture.

On the basis of application, the stem cells market is bifurcated into regenerative medicine and drug discovery and development. Regenerative medicine, which holds the larger share in the stem cells market, covers major disciplines such as orthopedics, hematology, wound care, diabetes, incontinence, neurology, oncology, cardiovascular and myocardial infarction, spinal cord injuries, and liver disorders.

Geographically, the global stem cells market is divided into Europe, Asia Pacific, North America, and Rest of the World. North America dominates the overall market, followed by Europe owing to increased prevalence of neurological and cardiac disorders, state initiatives and provision of grants from several organizations, development of innovative therapies, strong research activities, and effective marketing solutions. The Asia Pacific stem cells market is anticipated to witness impressive growth over the next two years thanks to rapidly growing contract research outsourcing and booming medical tourism.

The leading companies profiled in the stem cells market report are Osiris Therapeutics, Advanced Cell Technology, Cellartis AB, Bioheart, Cellular Engineering Technologies, Biotime Inc., Cytori Therapeutics Inc., Angel Biotechnology, Stemcelltechnologies Inc., California Stem Cell Inc., Brainstorm Cell Therapeutics, and Celgene Corporation Inc. These players are analyzed based on aspects such as company and financial overview, product portfolio, business strategies, and recent developments.

Global Stem Cells Market, By Product

Adult Stem Cells Hematopoietic Stem Cells Mesenchymal Stem Cells Neuronal Stem Cells Dental Stem Cells Umbilical Cord Stem Cells Human Embryonic Stem Cells Induced Pluripotent Stem Cells Rat Neural Stem Cells Very Small Embryonic-Like Stem Cells Global Stem Cells Market, By Technology

Stem Cell Acquisition Bone Marrow Harvest for Stem Cells Apheresis for Stem Cells Umbilical Cord Blood Stem Cell Production Therapeutic Cloning for Stem Cells Stem Cells Production By In Vitro Fertilization Stem Cell Isolation Stem Cell Culture Stem Cell Cryopreservation Stem Cells Expansion and Sub-Culture Global Stem Cells Market, By Application

Regenerative Medicine Neurology Orthopedics Oncology Hematology Cardiovascular and Myocardial Infarction Injuries Diabetes Liver Disorders Incontinence Others Drug Discovery and Development Global Stem Cells Market, By Geography

North America Asia Pacific Europe Rest of the World

Download Exclusive Brochure of This Report : http://www.transparencymarketresearch.com/sample/sample.php?flag

About Us

Transparency Market Research (TMR) is a global market intelligence company providing business information reports and services. The companys exclusive blend of quantitative forecasting and trend analysis provides forward-looking insight for thousands of decision makers. TMRs experienced team of analysts, researchers, and consultants use proprietary data sources and various tools and techniques to gather and analyze information.

TMRs data repository is continuously updated and revised by a team of research experts so that it always reflects the latest trends and information. With extensive research and analysis capabilities, Transparency Market Research employs rigorous primary and secondary research techniques to develop distinctive data sets and research material for business reports.

Contact

Mr.Sudip S 90 State Street, Suite 700 Albany, NY 12207 Tel: +1-518-618-1030 USA Canada Toll Free: 866-552-3453 Email: sales@transparencymarketresearch.com Website: http://www.transparencymarketresearch.com

This release was published on openPR.

See the article here:
Stem Cells Market Share, Size, Growth & Forecast 2018 Illuminated by New Report - Satellite PR News (press release)

Scientists are one step closer to mimicking the way biological systems interact and process information in the body -- a vital step toward developing new forms of biorobotics and novel treatment approaches for several muscle-related health problems such as muscular degenerative disorders, arrhythmia and limb loss.

Using cardiac muscle cells and cardiac fibroblasts -- cells found in connective heart tissue -- researchers at the University of Notre Dame have created a "living diode," which can be used for cell-based information processing, according to a recent study in Advanced Biosystems. Bioengineers created the muscle-based circuitry through a novel, self-forming, micro patterning approach.

Using muscle cells opens the door to functional, biological structures or "computational tissues" that would allow an organ to control and direct mechanical devices in the body. The design arranges the two types of cells in a rectangular pattern, separating excitable cells from nonexcitable cells, allowing the team to transduce electrical signals unidirectionally and achieve a diode function using living cells. In addition to the diode-like function, the natural pacing ability of the muscle cells allowed Pinar Zorlutuna, assistant professor of aerospace and mechanical engineering, and her team to pass along information embedded in the electrical signals by modulating the frequency of the cells' electrical activity. Zorlutuna's research was funded by the National Science Foundation.

"Muscle cells have the unique ability to respond to external signals while being connected to fibroblasts internally through intercellular junctions. By combining these two cell types, we have the ability to initiate, amplify and propagate signals directionally," said Zorlutuna, who is also director of the Tissue Engineering Laboratory at the university. "The success of these muscle-cell diodes offers a path toward linking such cell-based circuitry to a living system -- and creating functional control units for biomedical engineering applications such as bioactuators or biosensors."

The team's work presents a new option in biocomputing, which has focused primarily on using gene circuitries of genetically modified single-cells or neuronal networks doped with chemical additives to create information processing systems. The single-cell options are slower to process information since they relay on chemical processes, and neuronal-based approaches can misfire signals, firing backward up to 10 percent of the time.

Zorlutuna explores biomimetic environments in order to understand and control cell behavior. She also studies cell-cell and cell-environment interactions through tissue and genetic engineering, and micro- and nanotechnology at the Notre Dame Center for Nano Science and Technology. She is a researcher at the University's Center for Stem Cells and Regenerative Medicine and the Harper Cancer Research Institute.

Story Source:

Materials provided by University of Notre Dame. Note: Content may be edited for style and length.

Read more here:
Researchers develop 'living diode' using cardiac muscle cells - Science Daily

On Feb. 2, Naomi Ng 16 donated peripheral blood stem cells at an outpatient clinic as part of the Be The Match donor program. She was matched after registering for Be The Match through the Andy Talley Bone Marrow Foundation.

You swab your cheek and you might save someones life, Ng said. Its so easy to register to be a donor that you dont think about the impact.

Ng was informed of the potential match in the fall of 2016 and completed initial blood work. Having graduated in May with a degree in Environmental Studies, she had just begun working for Amtrak in D.C. as senior service planner. She was not contacted again until mid-December, and completed the non-surgical procedure several weeks later.

The Andy Talley Bone Marrow Foundation, a non-profit created in 2010 by the recently retired head football coach. Talley began promoting awareness about bone marrow donation in 1992 by hosting testing opportunities on campus. In 2008, he partnered with Be The Match to form the Get in the Game. Save a Life initiative. The foundation has now enlisted over 78 college football programs to participate in the foundations mission, registering young, healthy college students with the Be the Match registry to increase the chances of finding a bone marrow match for patients diagnosed with blood cancer.

Like many University students Ng registered at one of Talleys on campus testing drives. She swabbed her cheek, filled out the paperwork and doubted that she would ever get a call. I kind of forget that I had registered for it, Ng said. I had hoped obviously, because I wouldnt have registered if I didnt want to do it. Its just such a slim chance.

The donation of peripheral blood stem cells is one of two methods for collecting the blood-forming cells that recipients need. For five days before the procedure, Ng was given injections of filgrastim to increase the number of stem cells in her blood. On the day of the procedure she was connected to a machine via a needle in one arm and her blood was run through the machine and returned to her body through the other arm.

Although the filgrastim injections were painful, Ng described the procedure as pretty non-invasive, saying, I actually slept through the procedure. When I woke up I was like, thats it? I can leave now?

Ngs match is a 66-year old man, but his age and gender are the only things she knows about him. A year after the procedure, Be The Match will help to facilitate contact between the two if desired by donor and recipient.

Its a really emotional experience, Ng said. Ive never met this guy. I dont know his name. I dont know anything about him, but I feel like I have an emotional connection to him now. I dont know yet, but I might have saved his life.

Follow this link:
Senior Becomes the Match to donate bone marrow and saves life - Villanovan (subscription)

Growing stem cells on carbon nitride sheets not only activates bone-related genes, but also releases calcium ions when exposed to red light.

Asian Scientist Newsroom | February 15, 2017 | In the Lab

AsianScientist (Feb. 15, 2017) - Light absorbing nanosheets could help bone regrowth, according to a study by researchers at the Ulsan National Institute of Science and Technology published in ACS Nano.

Human bone marrow-derived mesenchymal stem cells (hBMSCs) have been successfully used to treat fractures by regenerating lost bone tissue. To increase the area of bone regeneration, scientists have attempted to enhance the function of stem cells using carbon nanotubes, graphenes and nano-oxides.

In the present study, Professors Kim Kwang S. and Suh Pann-Ghill examined the bone regenerative abilities of carbon nitride (C3N4) nanosheets. Firstly, Kim's team synthesized carbon nitrogen derivatives from melamine compounds. Then, they analyzed the light-absorbing characteristics of C3N4 sheets at a wavelength range of 455-635 nanometers (nm).

They found that the C3N4 sheets emit fluorescence at the wavelength of 635 nm when exposed to red light in a liquid state. The released electrons induced calcium to accumulate in the cytoplasm, thereby speeding up bone regeneration.

Suh's team then conducted studies investigating biomedical applications of this material. To do so, they cultured stem cells and cancer cells in a medium containing 200 g/ml of C3N4 sheets. The material showed no cytotoxicity after two days of testing, suggesting that it is biocompatible.

They also confirmed that C3N4 sheets induce stem cells to differentiate into osteoblasts to promote mineral formation, turning on osteogenic differentiation marker genes such as ALP, BSP, and OCN. Moreover, Runx2 (Runt-related transcription factor 2), a key transcription factor in osteoblast differentiation was also activated. This gene activation resulted in the increased osteoblast differentiation and accelerated bone formation.

This research has opened up the possibility of developing a new medicine that effectively treats skeletal injuries, such as fractures and osteoporosis, said co-author Professor Seo Young-Kyo. It will be a very useful tool for making artificial joints and teeth with the use of 3D printing.

This is an important milestone in the analysis of biomechanical functions needed for the development of biomaterials, including adjuvants for hard tissues such as damaged bones and teeth.

The research team expects that their findings affirm the potential of C3N4 sheets in developing bone formation and directing hBMSCs toward bone regeneration.

The article can be found at: Tiwari et al. (2016) Accelerated Bone Regeneration by Two-Photon Photoactivated Carbon Nitride Nanosheets.

Source: Ulsan National Institute of Science and Technology. Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

More here:
Lights, Carbon Nitride, Bone Regeneration! - Asian Scientist Magazine

Home Bone Health Stem cell technique may aid in bone repair

A new method for repairing damaged bones with stem cell and carbon material has been developed by researchers working with the Ulsan National Institute of Science and Technology (UNIST). The method involves using stem cells from human bone marrow and carbon sheets with photocatalytic properties, and may help to create better treatments for bone injuries like periodontal disease and fractures.

During their study, researchers found that carbon nitride sheets that absorb red light encourage proliferation and growth of bone, as well as osteogenic differentiation. Human bone marrow stem cells have previously been used in the treatment of fractures, as they promote bone regeneration even in patients who have lost large areas of bone because of trauma or disease. The use of carbon nitride sheets alongside the bone marrow stem cells in this study were an attempt to accelerate the regeneration process.

Researchers found that when the carbon nitride was exposed to red light, it absorbed the light and emitted fluorescence, which is already known to expedite bone regeneration. The study also showed proliferation in osteogenic differentiation genes and accelerated bone formation in cells that were cultured in the lab.

This new stem cell research shows that coupling human bone marrow stem cells with carbon nitride could prove to be an effective way to create new bone material in areas that are lacking. With further research, this method could soon be applied to helping to heal bone fractures and wear-and-tear related to diseases like osteoporosis, as well as used to create new joints and teeth.

Related: Improve bone density and reduce the risk of osteoporosis with lifestyle changes

Related Reading:

Eat these foods for strong bones

Six tips to improve your bone health

New Stem Cell Technique Shows Promise for Bone Repair

Follow this link:
Stem cell technique may aid in bone repair - Bel Marra Health

When three Southern Arkansas University nursing students started organizing this weeks stem cell registry drive more than three months ago, they were not aware that a member of the Mulerider family is one of more than 1,400 whose life could be saved.

The stem cell/bone marrow registry drive is scheduled for 9 a.m.-3:30 p.m. on Tuesday and Wednesday both in the Reynolds Center Rotunda and the SAU Baptist Collegiate Ministry.

For more information, contact Dr. Becky Parnell at (870)235-4365 or at bbparnell@saumag.edu .

The SAU BSN students initially behind the project are Renee Langley, Tabitha Elliott and Courtney Owens. Parnell explained that while attending the Arkansas Student Nurses Association annual meeting in Little Rock, the students were introduced to the need for bone marrow donors. They even registered to be possible donors themselves.

Parnell said they realized this project was a perfect example of how nurses can impact the care of people outside the normal hospitalized patient.

They recognized how many people this could potentially impact and wanted to recruit more people (to register), said Parnell. I have seen the bone marrow process it is truly a life-saving intervention for many people that are devastated by leukemia.

When Parnell began promoting the registry event on campus, it was brought to her attention that Sydney Galway, the daughter of a Magnolia native, 1984 SAU alum and Board of Governors Chair Beth Galway, is suffering with acute myeloid leukemia.

Sydney Galway is in dire need of a bone marrow transplant.

When Sydney was diagnosed with acute myeloid leukemia, the doctors told us that Sydneys only cure would come from a bone marrow transplant. The doctors were, and are, confident of the success of her treatment due to the fact that she has a high chance to find a perfect bone marrow donor, said Galway.

Her increased chance of finding a match, Galway explained, is simply because she is a Caucasian female which has one of the highest bone marrow donor rates. She has a 97 percent chance to find a donor.

Of course, the first donor they looked at was her sister. A sibling has only a 25 percent chance to be a match; a parent even less. Sydneys sister was not a match, said Galway.

Donor matches are generally based on race. With todays diverse community, the need for bone marrow donors from minority and mixed race groups is high. An African American patient has only a 66 percent chance to find a match.

The doctors and nurses that I have talked to indicate that the need is huge for African Americans as well as donors from India, said Galway.

She said that the treatment for Sydney, who is a sophomore in college, is now in phase 3. Her next step is a bone marrow transplant.

We hope to have a perfect match for her and pray that the donor will be willing to do all that is necessary for providing the blood or bone marrow needed for the transplant, said Galway.

The drive is being sponsored by SAUs Department of Nursing and University Health Services. Junior and senior BSN students will also be assisting in the bone marrow drive as a professional development activity.

Becoming a member of a stem cell/bone marrow registry only requires that you provide a swab of the cells inside your cheek. To register is a painless and fast way to possibly save a life.

See the original post here:
Stem cell registry drive at SAU seeks to connect potential donors with people who need help - Magnoliareporter