2. Bone Marrow (Hematopoietic) Stem Cells [Stem Cell Information]
By LizaAVILA
by Jos Domen*, Amy Wagers** and Irving L. Weissman***
Blood and the system that forms it, known as the hematopoietic system, consist of many cell types with specialized functions (see Figure 2.1). Red blood cells (erythrocytes) carry oxygen to the tissues. Platelets (derived from megakaryocytes) help prevent bleeding. Granulocytes (neutrophils, basophils and eosinophils) and macrophages (collectively known as myeloid cells) fight infections from bacteria, fungi, and other parasites such as nematodes (ubiquitous small worms). Some of these cells are also involved in tissue and bone remodeling and removal of dead cells. B-lymphocytes produce antibodies, while T-lymphocytes can directly kill or isolate by inflammation cells recognized as foreign to the body, including many virus-infected cells and cancer cells. Many blood cells are short-lived and need to be replenished continuously; the average human requires approximately one hundred billion new hematopoietic cells each day. The continued production of these cells depends directly on the presence of Hematopoietic Stem Cells (HSCs), the ultimate, and only, source of all these cells.
Figure 2.1. Hematopoietic and stromal cell differentiation.
2001 Terese Winslow (assisted by Lydia Kibiuk)
The search for stem cells began in the aftermath of the bombings in Hiroshima and Nagasaki in 1945. Those who died over a prolonged period from lower doses of radiation had compromised hematopoietic systems that could not regenerate either sufficient white blood cells to protect against otherwise nonpathogenic infections or enough platelets to clot their blood. Higher doses of radiation also killed the stem cells of the intestinal tract, resulting in more rapid death. Later, it was demonstrated that mice that were given doses of whole body X-irradiation developed the same radiation syndromes; at the minimal lethal dose, the mice died from hematopoietic failure approximately two weeks after radiation exposure.1 Significantly, however, shielding a single bone or the spleen from radiation prevented this irradiation syndrome. Soon thereafter, using inbred strains of mice, scientists showed that whole-body-irradiated mice could be rescued from otherwise fatal hematopoietic failure by injection of suspensions of cells from blood-forming organs such as the bone marrow.2 In 1956, three laboratories demonstrated that the injected bone marrow cells directly regenerated the blood-forming system, rather than releasing factors that caused the recipients' cells to repair irradiation damage.35 To date, the only known treatment for hematopoietic failure following whole body irradiation is transplantation of bone marrow cells or HSCs to regenerate the blood-forming system in the host organisms.6,7
The hematopoietic system is not only destroyed by the lowest doses of lethal X-irradiation (it is the most sensitive of the affected vital organs), but also by chemotherapeutic agents that kill dividing cells. By the 1960s, physicians who sought to treat cancer that had spread (metastasized) beyond the primary cancer site attempted to take advantage of the fact that a large fraction of cancer cells are undergoing cell division at any given point in time. They began using agents (e.g., chemical and X-irradiation) that kill dividing cells to attempt to kill the cancer cells. This required the development of a quantitative assessment of damage to the cancer cells compared that inflicted on normal cells. Till and McCulloch began to assess quantitatively the radiation sensitivity of one normal cell type, the bone marrow cells used in transplantation, as it exists in the body. They found that, at sub-radioprotective doses of bone marrow cells, mice that died 1015 days after irradiation developed colonies of myeloid and erythroid cells (see Figure 2.1 for an example) in their spleens. These colonies correlated directly in number with the number of bone marrow cells originally injected (approximately 1 colony per 7,000 bone marrow cells injected).8 To test whether these colonies of blood cells derived from single precursor cells, they pre-irradiated the bone marrow donors with low doses of irradiation that would induce unique chromosome breaks in most hematopoietic cells but allow some cells to survive. Surviving cells displayed radiation-induced and repaired chromosomal breaks that marked each clonogenic (colony-initiating) hematopoietic cell.9 The researchers discovered that all dividing cells within a single spleen colony, which contained different types of blood cells, contained the same unique chromosomal marker. Each colony displayed its own unique chromosomal marker, seen in its dividing cells.9 Furthermore, when cells from a single spleen colony were re-injected into a second set of lethally-irradiated mice, donor-derived spleen colonies that contained the same unique chromosomal marker were often observed, indicating that these colonies had been regenerated from the same, single cell that had generated the first colony. Rarely, these colonies contained sufficient numbers of regenerative cells both to radioprotect secondary recipients (e.g., to prevent their deaths from radiation-induced blood cell loss) and to give rise to lymphocytes and myeloerythroid cells that bore markers of the donor-injected cells.10,11 These genetic marking experiments established the fact that cells that can both self-renew and generate most (if not all) of the cell populations in the blood must exist in bone marrow. At the time, such cells were called pluripotent HSCs, a term later modified to multipotent HSCs.12,13 However, identifying stem cells in retrospect by analysis of randomly chromosome-marked cells is not the same as being able to isolate pure populations of HSCs for study or clinical use.
Achieving this goal requires markers that uniquely define HSCs. Interestingly, the development of these markers, discussed below, has revealed that most of the early spleen colonies visible 8 to 10 days after injection, as well as many of the later colonies, visible at least 12 days after injection, are actually derived from progenitors rather than from HSCs. Spleen colonies formed by HSCs are relatively rare and tend to be present among the later colonies.14,15 However, these findings do not detract from Till and McCulloch's seminal experiments to identify HSCs and define these unique cells by their capacities for self-renewal and multilineage differentiation.
While much of the original work was, and continues to be, performed in murine model systems, strides have been made to develop assays to study human HSCs. The development of Fluorescence Activated Cell Sorting (FACS) has been crucial for this field (see Figure 2.2). This technique enables the recognition and quantification of small numbers of cells in large mixed populations. More importantly, FACS-based cell sorting allows these rare cells (1 in 2000 to less than 1 in 10,000) to be purified, resulting in preparations of near 100% purity. This capability enables the testing of these cells in various assays.
Figure 2.2. Enrichment and purification methods for hematopoietic stem cells. Upper panels illustrate column-based magnetic enrichment. In this method, the cells of interest are labeled with very small iron particles (A). These particles are bound to antibodies that only recognize specific cells. The cell suspension is then passed over a column through a strong magnetic field which retains the cells with the iron particles (B). Other cells flow through and are collected as the depleted negative fraction. The magnet is removed, and the retained cells are collected in a separate tube as the positive or enriched fraction (C). Magnetic enrichment devices exist both as small research instruments and large closed-system clinical instruments.
Lower panels illustrate Fluorescence Activated Cell Sorting (FACS). In this setting, the cell mixture is labeled with fluorescent markers that emit light of different colors after being activated by light from a laser. Each of these fluorescent markers is attached to a different monoclonal antibody that recognizes specific sets of cells (D). The cells are then passed one by one in a very tight stream through a laser beam (blue in the figure) in front of detectors (E) that determine which colors fluoresce in response to the laser. The results can be displayed in a FACS-plot (F). FACS-plots (see figures 3 and 4 for examples) typically show fluorescence levels per cell as dots or probability fields. In the example, four groups can be distinguished: Unstained, red-only, green-only, and red-green double labeling. Each of these groups, e.g., green fluorescence-only, can be sorted to very high purity. The actual sorting happens by breaking the stream shown in (E) into tiny droplets, each containing 1 cell, that then can be sorted using electric charges to move the drops. Modern FACS machines use three different lasers (that can activate different set of fluorochromes), to distinguish up to 8 to 12 different fluorescence colors and sort 4 separate populations, all simultaneously.
Go here to read the rest:
2. Bone Marrow (Hematopoietic) Stem Cells [Stem Cell Information]
- 001 Expansion of Stem Cells by Valproic Acid [Last Updated On: June 24th, 2011] [Originally Added On: June 24th, 2011]
- 002 Cord Blood and Bone Marrow Stem Cells for Liver Failure [Last Updated On: June 25th, 2011] [Originally Added On: June 25th, 2011]
- 003 Science behind Enhancing Adult Stem Cells for wellbeing [Last Updated On: June 26th, 2011] [Originally Added On: June 26th, 2011]
- 004 Stem cells Transplatation in Completed Paralyze Dog. [Last Updated On: June 26th, 2011] [Originally Added On: June 26th, 2011]
- 005 STEM CELLS - Bone Marrow Stem Cells (Balzitt).flv [Last Updated On: June 27th, 2011] [Originally Added On: June 27th, 2011]
- 006 Bone Marrow Stem Cells/Gene Therapy [Last Updated On: June 28th, 2011] [Originally Added On: June 28th, 2011]
- 007 Stem cells used for medical treatment [Last Updated On: June 30th, 2011] [Originally Added On: June 30th, 2011]
- 008 STEM CELLS FOR OTHER USES Interview with Sam Smith.wmv [Last Updated On: July 1st, 2011] [Originally Added On: July 1st, 2011]
- 009 Stem Cells Reversing Endothelial Senescence [Last Updated On: July 2nd, 2011] [Originally Added On: July 2nd, 2011]
- 010 Bone Marrow Stem Cells [Last Updated On: July 3rd, 2011] [Originally Added On: July 3rd, 2011]
- 011 Bone marrow transplantation HD, ENG subtitles [Last Updated On: July 5th, 2011] [Originally Added On: July 5th, 2011]
- 012 Adult Stem Cells May Target and Repair Heart Attack Damage [Last Updated On: July 6th, 2011] [Originally Added On: July 6th, 2011]
- 013 Bone Marrow Stem Cell Applications [Last Updated On: July 8th, 2011] [Originally Added On: July 8th, 2011]
- 014 Stem cells in bone marrow are being used to treat EB [Last Updated On: July 13th, 2011] [Originally Added On: July 13th, 2011]
- 015 STEM CELLS FOR MACULAR DEGENERATION Sam Smith's story.wmv [Last Updated On: July 14th, 2011] [Originally Added On: July 14th, 2011]
- 016 MS Cure - Progression [Last Updated On: July 14th, 2011] [Originally Added On: July 14th, 2011]
- 017 Blind Girl get's cure you need to see to believe" [Last Updated On: July 17th, 2011] [Originally Added On: July 17th, 2011]
- 018 From Surgical Repair to Stem Cell Repair: A Surgeon's Journey by Leonard Smith MD, FACS [Last Updated On: July 19th, 2011] [Originally Added On: July 19th, 2011]
- 019 Bone Marrow Stem Cell Donation [Last Updated On: July 19th, 2011] [Originally Added On: July 19th, 2011]
- 020 The potential of stem cells [Last Updated On: July 28th, 2011] [Originally Added On: July 28th, 2011]
- 021 LifeCell in Kalaignar Seithigal,Sun News [Last Updated On: July 31st, 2011] [Originally Added On: July 31st, 2011]
- 022 Spirulina DLA Naturals [Last Updated On: August 6th, 2011] [Originally Added On: August 6th, 2011]
- 023 Bill Lahti; stem cell nutrition stimulates wound repair for diabetic stroke victim [Last Updated On: August 6th, 2011] [Originally Added On: August 6th, 2011]
- 024 Christian Drapeau Talk About - Adult Stem Cells and StemEnhance./StemTech [Last Updated On: August 7th, 2011] [Originally Added On: August 7th, 2011]
- 025 "Bone Marrow Stem Cells" Donald Kohn [Last Updated On: August 14th, 2011] [Originally Added On: August 14th, 2011]
- 026 Cancer Update: Autologus Stem Cell (Bone Marrow) Transplant [Last Updated On: September 4th, 2011] [Originally Added On: September 4th, 2011]
- 027 Bone Marrow / Stem Cell Transplant Recovery Fund [Last Updated On: September 6th, 2011] [Originally Added On: September 6th, 2011]
- 028 Bone Marrow/Stem Cell Transplantation: An Introduction, With Sonali Smith, MD [Last Updated On: September 9th, 2011] [Originally Added On: September 9th, 2011]
- 029 Bone Marrow Stem Cell Transplant Live from Top US Hospital [Last Updated On: September 12th, 2011] [Originally Added On: September 12th, 2011]
- 030 Adult Stem Cell Mobilization from Bone Marrow (Animation) [Last Updated On: September 12th, 2011] [Originally Added On: September 12th, 2011]
- 031 MS Cure - Introduction to stem cell bone marrow transplant in Australia [Last Updated On: September 13th, 2011] [Originally Added On: September 13th, 2011]
- 032 Immune Modulation by Bone Marrow Mesenchymal Stem Cells [Last Updated On: September 14th, 2011] [Originally Added On: September 14th, 2011]
- 033 Bone Marrow/Stem Cell Transplant [Last Updated On: September 15th, 2011] [Originally Added On: September 15th, 2011]
- 034 Bone Marrow and Stem Cell Transplant Patients Share Their Stories [Last Updated On: September 20th, 2011] [Originally Added On: September 20th, 2011]
- 035 Stem Cell Transplant India,Bone Marrow Transplant India,Sickle Cell Anemia Treatment India [Last Updated On: September 20th, 2011] [Originally Added On: September 20th, 2011]
- 036 Bone Marrow Stem Cell Expansion by HOXB4 and p21 Knock Out [Last Updated On: September 21st, 2011] [Originally Added On: September 21st, 2011]
- 037 Multiple Sclerosis, Stem Cells, and Hope, Part 2 [Last Updated On: September 22nd, 2011] [Originally Added On: September 22nd, 2011]
- 038 Becoming a Blood Stem Cell Donor [Last Updated On: September 24th, 2011] [Originally Added On: September 24th, 2011]
- 039 LittleBigPlanet 2 - Stem Cell Sackboy Quarter 4 Update (Bone Marrow Bugaloo) [Last Updated On: September 25th, 2011] [Originally Added On: September 25th, 2011]
- 040 Can Stem Cell Prolotherapy or Bone Marrow Prolotherapy help articular cartilage defects? [Last Updated On: September 27th, 2011] [Originally Added On: September 27th, 2011]
- 041 Mesenchymal stem cells and marrow stromal cells [Last Updated On: October 1st, 2011] [Originally Added On: October 1st, 2011]
- 042 Bone Marrow Transplant and Stem Cell Transplant Treatment in India for International patients [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 043 Bone Marrow Stem Cell Aspiration and Re-Injection with PRP for Osteoarthritis by Dr Adelson [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 044 Selected Donor for Stem Cell, Bone Marrow [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 045 Stem Cell Injections - Bone Marrow Prolotherapy - treatment for arthritis [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 046 Nurses Discuss Special Bonds With Bone Marrow and Stem Cell Transplant Patients [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 047 Hagen's bone marrow collection part 1 [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 048 Samsparks after bone marrow collection for stem cell treatm [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 049 Chat w/ Dr. Maharaj, founder of S. FL. Bone Marrow/Stem Cell Transplant Institute [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 050 Bone Marrow - Stem Cell Prolotherapy [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 051 MS Cure - Hickman line Insertion for stem cell/bone marrow transplant [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 052 Bone Marrow Transplant Program Continues to Grow, Make a Difference [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 053 Stem cell transplant in children: what to expect | Dana-Farber Cancer Institute [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 054 LittleBigPlanet 2 - (WIP) Stem Cell Sackboy Bone Marrow Bugaloo [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 055 Calum's stem cell donation for Anthony Nolan [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 056 Stem Cell Treatment in New Jersey- Colon's story (Dr Damon Noto) [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 057 How to be an Anthony Nolan blood stem cell donor [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 058 Dr Steve talks about stem cells.mov [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 059 Stem Cells extracted from bone marrow [Last Updated On: October 6th, 2011] [Originally Added On: October 6th, 2011]
- 060 Webinar 1, Stem cell therapy basics, what is available today? [Last Updated On: October 6th, 2011] [Originally Added On: October 6th, 2011]
- 061 Mesenchymal stem cells and marrow stromal cells---2nd--- [Last Updated On: October 8th, 2011] [Originally Added On: October 8th, 2011]
- 062 Harvesting stem cells from horse bone marrow at UT [Last Updated On: October 12th, 2011] [Originally Added On: October 12th, 2011]
- 063 Bone Marrow Stem Cells - Video [Last Updated On: October 13th, 2011] [Originally Added On: October 13th, 2011]
- 064 Stem Cell Transplant Apheresis Method - Video [Last Updated On: October 14th, 2011] [Originally Added On: October 14th, 2011]
- 065 Mantak Chia: Sumup stem cell (Berlin,Germany 2009) Part I : Bone marrow activate Stem cell - Video [Last Updated On: October 16th, 2011] [Originally Added On: October 16th, 2011]
- 066 Stem Cell, Bone Marrow Transplants / Donations - Easy and life saving proceedure - Video [Last Updated On: October 18th, 2011] [Originally Added On: October 18th, 2011]
- 067 HIV/AIDS: Spotlight on Stem Cell Research - Loren Leeds - Video [Last Updated On: October 21st, 2011] [Originally Added On: October 21st, 2011]
- 068 Sickle Cell Anemia: Stem Cell Gene Therapy - Donald Kohn - Video [Last Updated On: October 21st, 2011] [Originally Added On: October 21st, 2011]
- 069 Do you need a large number of stem cells injected for Bone Marrow Prolotherapy to work? - Video [Last Updated On: October 23rd, 2011] [Originally Added On: October 23rd, 2011]
- 070 What are stem cells? - Video [Last Updated On: October 27th, 2011] [Originally Added On: October 27th, 2011]
- 071 What is in situ Stem Cell Injection Therapy or Bone Marrow Prolotherapy? - Video [Last Updated On: October 27th, 2011] [Originally Added On: October 27th, 2011]
- 072 Stem Cells Research at Hadassah - Video [Last Updated On: October 27th, 2011] [Originally Added On: October 27th, 2011]
- 073 Blood or Bone Marrow Cells May Provide a Route to Healing Blood Vessels - Video [Last Updated On: October 27th, 2011] [Originally Added On: October 27th, 2011]
- 074 Hematopoietic stem cell transplantation #2 - Video [Last Updated On: October 28th, 2011] [Originally Added On: October 28th, 2011]
- 075 Radiation - Sickle Cell Half Match Stem Cell Bone Marrow Transplant 2 - Video [Last Updated On: November 7th, 2011] [Originally Added On: November 7th, 2011]
- 076 Sickle Cell Stem Cell Bone Marrow Transplant 3 - Video [Last Updated On: November 7th, 2011] [Originally Added On: November 7th, 2011]
- 077 Macular degeneration - Stem Cell therapy (English subtitles) - Video [Last Updated On: November 13th, 2011] [Originally Added On: November 13th, 2011]
- 078 Where Do The Stem Cells Come From? Hollywood | Los Angeles - Video [Last Updated On: November 13th, 2011] [Originally Added On: November 13th, 2011]
- 079 Bone Marrow Stem Cell Injections - Video [Last Updated On: November 14th, 2011] [Originally Added On: November 14th, 2011]
- 080 Diabetes- Stem cell therapy (english) - Video [Last Updated On: December 2nd, 2011] [Originally Added On: December 2nd, 2011]
