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Research on the effects of stem cell source and patient age on transplantation outcomes
December 08, 2008Two studies examining the effects of stem cell source and patient age on stem cell transplantation outcomes will be explored at a press conference taking place on Sunday, December 7, at 8:00 a.m., during the 50th Annual Meeting of the American Society of Hematology in San Francisco, CA. Preliminary results from a study examining a specialized technique for increasing the presence of stem cells in cord blood for transplantation will also be shared during the press conference.
"For years, stem cell transplants have been a standard treatment option for many blood cancers and other hematologic conditions," said Armand Keating, MD, moderator of the press conference and Director, Division of Hematology, and Professor of Medicine at the University of Toronto, Ontario, Canada. "The results of these studies add to the growing body of knowledge about the best regimens available to help produce durable responses and prolonged survival in many groups of patients."
Blood cancers - leukemia, lymphoma, and myeloma - are typically treated with a combination of treatments including chemotherapy, biological therapy, radiation therapy, and stem cell transplantation. Stem cell transplantation is the process by which blood stem cells are collected from a donor, or from the patient prior to chemotherapy, and then infused into the patient after treatment. The transplanted stem cells travel to the bone marrow and begin to produce new blood cells, replacing those that are destroyed as a side effect of chemotherapy. Stem cell transplants are categorized by the source of the stem cells (bone marrow, peripheral blood, or cord blood) and by their origin - autologous (from the patient) or allogeneic (from a donor).
Effect of Stem Cell Source on Transplant Outcomes in Adults With Acute Leukemia: A Comparison of Unrelated Bone Marrow, Peripheral Blood, and Cord Blood [Abstract #151]
Mary Eapen, MBBS, the Center for International Blood and Marrow Transplantation along with the European Group for Blood and Marrow Transplantation and the New York Blood Center
In the absence of a matched sibling donor, the first choice for stem cell transplantation for patients with acute leukemia is an unrelated adult donor whose tissue type matches that of the patient. However, when such a donor is not available, the researchers of this study found that mismatched unrelated cord blood transplants were a suitable alternative to mismatched bone marrow or peripheral blood transplants because cord blood is readily available, making it an ideal option when transplantation is needed urgently.
For successful transplantation, bone marrow and peripheral blood donors are examined for genetic compatibility with the patient by comparing their human leukocyte antigens (HLAs). Current estimates from the National Marrow Donor Program donor registry suggest that the probability of finding a matched unrelated adult donor is relatively low (51 percent for Caucasians, 30 percent for Hispanics, 20 percent for Asians, and 17 percent for African Americans).
Cord blood donated to public cord blood banks can be an alternative source of stem cells for patients who need a transplant but cannot find a matched adult donor. The matching requirements for cord blood are not as strict as for bone marrow or peripheral blood because cord blood cells are immunologically immature and therefore more tolerant to mismatching.
The purpose of this study was to determine the efficacy of three types of stem cell sources: bone marrow, peripheral blood, and cord blood. Study results were based on an analysis of the outcomes of 1,240 adults with acute leukemia (707 patients with acute myeloid leukemia and 533 patients with acute lymphocytic leukemia) from 2002 to 2006. Of those patients who received a bone marrow stem cell transplant, 243 were matched at eight out of eight possible HLA loci and 111 were matched at seven HLA loci. In those receiving a peripheral blood stem cell transplant, 518 were matched at eight HLA loci and 210 at seven HLA loci. In those receiving cord blood transplants, 28 were matched at five or six HLA loci and 110 matched at four HLA loci.
The study found that there were fewer transplant-related deaths for matched peripheral blood and bone marrow transplants (27 percent and 26 percent, respectively) than as for mismatched peripheral blood, bone marrow, and cord blood transplants (42 percent, 37 percent, and 41 percent, respectively). Leukemia-free survival (LFS) and overall survival (OS) were highest after transplantation of matched peripheral blood (LFS: 43 percent; OS: 45 percent) and bone marrow (LFS: 46 percent; OS: 48 percent). These rates were lower after transplantation of mismatched peripheral blood (LFS: 33 percent; OS: 36 percent), bone marrow (LFS: 34 percent; OS: 38 percent), and cord blood (LFS: 33 percent; OS: 35 percent). Importantly, rates of transplant-related deaths, leukemia-free survival, and overall survival for the three types of mismatched transplants were similar even though cord blood transplants were mismatched at more HLA loci.
Notch-Mediated Expansion of Human Cord Blood Progenitor Cells Results in Rapid Myeloid Reconstitution in Vivo Following Myeloablative Cord Blood Transplantation [Abstract #212]
Colleen Delaney, MD, Fred Hutchinson Cancer Research Center, Seattle, WA
This phase I study found that cord blood that is cultured to increase the number of CD34+ stem cells prior to transplantation helped to decrease the time to engraftment in patients with acute myeloid leukemia.
Cord blood is a valuable source of hematopoietic stem cells as it has a higher concentration of these cells than is normally found in adult blood. However, as only a small quantity of blood can typically be obtained from an umbilical cord, resulting in fewer available stem cells for transplantation, researchers have been investigating novel methods to expand the number of stem cells available from cord blood to help increase the success rates of cord blood stem cell transplants.
The objective of this study is to evaluate the safety and potential efficacy of giving increased numbers of cord blood progenitor cells that have been generated through a novel methodology whereby CD34+ cord blood progenitor cells are cultured prior to infusion to rapidly multiply in order to decrease the time required for the transplanted cells to engraft and begin production of healthy blood cells.
A total of six patients with acute myeloid leukemia were treated with a transplantation-preparation regimen of cytoxan (120 mg/kg), fludarabine (75 mg/m2), and TBI (1320 cGy), followed one day later by an infusion of one unit of non-cultured cord blood and one unit of cord blood that had been CD34+ enriched and cultured for 16 days. The non-cultured unit was given to provide long-term repopulating stem cells that had not been previously manipulated, while the goal of the expanded unit was to provide cells capable of rapid myeloid recovery.
To achieve best results, cord blood units that most closely genetically matched the patient were selected for transfusion. All non-cultured cord blood stem cells were matched for four out of six alleles for each patient. For the cultured cord blood cells, two patients received a five-out-of-six allele match and four patients received a four-out-of-six allele match. There was an average CD34+ increase of 160 (range 41 to 382), meaning that for every one CD34+ cell, there were 160 CD34+ cells after the culture, with an average total nucleated cell fold increase of 660 (range 146 to 1496). A control group of 17 patients underwent an identical transplant regimen, but received two non-cultured cord blood units.
A relatively rapid engraftment time, averaging 14 days, was observed in the six patients in the experimental group compared with 25 days for the patients in the control group. The contribution of the expanded and non-cultured cord blood cells was determined by a DNA-based assay beginning seven days following the transplant. In the five patients with early engraftment, the engrafted cells present at day seven were derived almost entirely from the cultured unit. Persistent contribution to engraftment from the cultured cells was noted in two patients. One patient had persistent contribution from the cultured cells through 280 days post-transplant that was no longer noticeable at one year, and the second patient continued to demonstrate contribution from the cultured cells at 180 days post-transplant. One patient died on day 462 from a rare complication of myelitis (inflammation of the spinal cord) caused by the varicella-zoster virus, while all other patients were still in remission.
Non-Myeloablative Hematopoietic Stem Cell Transplantation in Older Patients With AML and MDS: Results From the Center for International Blood and Marrow Transplant Research (CIBMTR) [Abstract #346]
Sergio Giralt, MD, The University of Texas M. D. Anderson Cancer Center, Houston, TX
This study found that the outcomes of adults over the age of 65 undergoing allogeneic stem cell transplantation for the treatment of acute myeloid leukemia and myelodysplastic syndromes were similar to younger adults even after adjusting for multiple risk factors. The researchers concluded that age alone should not be a limiting factor for proceeding to allogeneic stem cell transplantation in these patients.
While stem cell transplantation remains one of the best treatment options for increasing overall survival and a possible cure for patients with acute myeloid leukemia and myelodysplastic syndromes, transplants generally are not given to patients over the age of 65 because of concerns about extreme toxicity and poor outcomes. Over the past few years, non-myeloablative transplants that require smaller and safer doses of chemotherapy and radiation have allowed stem cell transplants to be conducted in older individuals or other patients considered too weak to withstand conventional stem cell treatment regimens.
To better study age as a predictor of outcome in patients receiving stem cell transplants, data from the Center for International Blood and Marrow Transplant Research (CIBMTR) on 565 patients with acute myeloid leukemia and 551 patients with myelodysplastic syndromes were retrospectively analyzed for transplant-related mortality, engraftment, incidence of acute and chronic graft-versus-host disease, leukemia-free survival, and overall survival. Outcome data gathered from 1995 to 2005 were stratified into four groups by patient age for comparison: ages 40 to 54, 54 to 59, 60 to 64, and 65 and older.
The analysis found that there was no statistically significant difference in transplant-related mortality across age groups, and no overall difference in the occurrence of acute graft-versus-host disease (31-35 percent at 100 days) or chronic graft-versus-host disease (36-53 percent at two years). Rates of relapse were similar across all age groups (29-30 percent at three years). Additionally, no statistically significant impact of age was found for transplant-related mortality, leukemia-free survival, or overall survival. Type of disease and disease status at transplant were significant risk factors for leukemia-free survival and overall survival at one year and for transplant-related mortality and relapse at two years. Patients' general health and degree of tissue-type match between recipient and donor were also significant at two years for nearly all outcomes.
American Society of Hematology
Effect of Stem Cell Source on Transplant Outcomes in Adults With Acute Leukemia: A Comparison of Unrelated Bone Marrow, Peripheral Blood, and Cord Blood [Abstract #151]
Mary Eapen, MBBS, the Center for International Blood and Marrow Transplantation along with the European Group for Blood and Marrow Transplantation and the New York Blood Center
In the absence of a matched sibling donor, the first choice for stem cell transplantation for patients with acute leukemia is an unrelated adult donor whose tissue type matches that of the patient. However, when such a donor is not available, the researchers of this study found that mismatched unrelated cord blood transplants were a suitable alternative to mismatched bone marrow or peripheral blood transplants because cord blood is readily available, making it an ideal option when transplantation is needed urgently.
For successful transplantation, bone marrow and peripheral blood donors are examined for genetic compatibility with the patient by comparing their human leukocyte antigens (HLAs). Current estimates from the National Marrow Donor Program donor registry suggest that the probability of finding a matched unrelated adult donor is relatively low (51 percent for Caucasians, 30 percent for Hispanics, 20 percent for Asians, and 17 percent for African Americans).
Cord blood donated to public cord blood banks can be an alternative source of stem cells for patients who need a transplant but cannot find a matched adult donor. The matching requirements for cord blood are not as strict as for bone marrow or peripheral blood because cord blood cells are immunologically immature and therefore more tolerant to mismatching.
The purpose of this study was to determine the efficacy of three types of stem cell sources: bone marrow, peripheral blood, and cord blood. Study results were based on an analysis of the outcomes of 1,240 adults with acute leukemia (707 patients with acute myeloid leukemia and 533 patients with acute lymphocytic leukemia) from 2002 to 2006. Of those patients who received a bone marrow stem cell transplant, 243 were matched at eight out of eight possible HLA loci and 111 were matched at seven HLA loci. In those receiving a peripheral blood stem cell transplant, 518 were matched at eight HLA loci and 210 at seven HLA loci. In those receiving cord blood transplants, 28 were matched at five or six HLA loci and 110 matched at four HLA loci.
The study found that there were fewer transplant-related deaths for matched peripheral blood and bone marrow transplants (27 percent and 26 percent, respectively) than as for mismatched peripheral blood, bone marrow, and cord blood transplants (42 percent, 37 percent, and 41 percent, respectively). Leukemia-free survival (LFS) and overall survival (OS) were highest after transplantation of matched peripheral blood (LFS: 43 percent; OS: 45 percent) and bone marrow (LFS: 46 percent; OS: 48 percent). These rates were lower after transplantation of mismatched peripheral blood (LFS: 33 percent; OS: 36 percent), bone marrow (LFS: 34 percent; OS: 38 percent), and cord blood (LFS: 33 percent; OS: 35 percent). Importantly, rates of transplant-related deaths, leukemia-free survival, and overall survival for the three types of mismatched transplants were similar even though cord blood transplants were mismatched at more HLA loci.
Notch-Mediated Expansion of Human Cord Blood Progenitor Cells Results in Rapid Myeloid Reconstitution in Vivo Following Myeloablative Cord Blood Transplantation [Abstract #212]
Colleen Delaney, MD, Fred Hutchinson Cancer Research Center, Seattle, WA
This phase I study found that cord blood that is cultured to increase the number of CD34+ stem cells prior to transplantation helped to decrease the time to engraftment in patients with acute myeloid leukemia.
Cord blood is a valuable source of hematopoietic stem cells as it has a higher concentration of these cells than is normally found in adult blood. However, as only a small quantity of blood can typically be obtained from an umbilical cord, resulting in fewer available stem cells for transplantation, researchers have been investigating novel methods to expand the number of stem cells available from cord blood to help increase the success rates of cord blood stem cell transplants.
The objective of this study is to evaluate the safety and potential efficacy of giving increased numbers of cord blood progenitor cells that have been generated through a novel methodology whereby CD34+ cord blood progenitor cells are cultured prior to infusion to rapidly multiply in order to decrease the time required for the transplanted cells to engraft and begin production of healthy blood cells.
A total of six patients with acute myeloid leukemia were treated with a transplantation-preparation regimen of cytoxan (120 mg/kg), fludarabine (75 mg/m2), and TBI (1320 cGy), followed one day later by an infusion of one unit of non-cultured cord blood and one unit of cord blood that had been CD34+ enriched and cultured for 16 days. The non-cultured unit was given to provide long-term repopulating stem cells that had not been previously manipulated, while the goal of the expanded unit was to provide cells capable of rapid myeloid recovery.
To achieve best results, cord blood units that most closely genetically matched the patient were selected for transfusion. All non-cultured cord blood stem cells were matched for four out of six alleles for each patient. For the cultured cord blood cells, two patients received a five-out-of-six allele match and four patients received a four-out-of-six allele match. There was an average CD34+ increase of 160 (range 41 to 382), meaning that for every one CD34+ cell, there were 160 CD34+ cells after the culture, with an average total nucleated cell fold increase of 660 (range 146 to 1496). A control group of 17 patients underwent an identical transplant regimen, but received two non-cultured cord blood units.
A relatively rapid engraftment time, averaging 14 days, was observed in the six patients in the experimental group compared with 25 days for the patients in the control group. The contribution of the expanded and non-cultured cord blood cells was determined by a DNA-based assay beginning seven days following the transplant. In the five patients with early engraftment, the engrafted cells present at day seven were derived almost entirely from the cultured unit. Persistent contribution to engraftment from the cultured cells was noted in two patients. One patient had persistent contribution from the cultured cells through 280 days post-transplant that was no longer noticeable at one year, and the second patient continued to demonstrate contribution from the cultured cells at 180 days post-transplant. One patient died on day 462 from a rare complication of myelitis (inflammation of the spinal cord) caused by the varicella-zoster virus, while all other patients were still in remission.
Non-Myeloablative Hematopoietic Stem Cell Transplantation in Older Patients With AML and MDS: Results From the Center for International Blood and Marrow Transplant Research (CIBMTR) [Abstract #346]
Sergio Giralt, MD, The University of Texas M. D. Anderson Cancer Center, Houston, TX
This study found that the outcomes of adults over the age of 65 undergoing allogeneic stem cell transplantation for the treatment of acute myeloid leukemia and myelodysplastic syndromes were similar to younger adults even after adjusting for multiple risk factors. The researchers concluded that age alone should not be a limiting factor for proceeding to allogeneic stem cell transplantation in these patients.
While stem cell transplantation remains one of the best treatment options for increasing overall survival and a possible cure for patients with acute myeloid leukemia and myelodysplastic syndromes, transplants generally are not given to patients over the age of 65 because of concerns about extreme toxicity and poor outcomes. Over the past few years, non-myeloablative transplants that require smaller and safer doses of chemotherapy and radiation have allowed stem cell transplants to be conducted in older individuals or other patients considered too weak to withstand conventional stem cell treatment regimens.
To better study age as a predictor of outcome in patients receiving stem cell transplants, data from the Center for International Blood and Marrow Transplant Research (CIBMTR) on 565 patients with acute myeloid leukemia and 551 patients with myelodysplastic syndromes were retrospectively analyzed for transplant-related mortality, engraftment, incidence of acute and chronic graft-versus-host disease, leukemia-free survival, and overall survival. Outcome data gathered from 1995 to 2005 were stratified into four groups by patient age for comparison: ages 40 to 54, 54 to 59, 60 to 64, and 65 and older.
The analysis found that there was no statistically significant difference in transplant-related mortality across age groups, and no overall difference in the occurrence of acute graft-versus-host disease (31-35 percent at 100 days) or chronic graft-versus-host disease (36-53 percent at two years). Rates of relapse were similar across all age groups (29-30 percent at three years). Additionally, no statistically significant impact of age was found for transplant-related mortality, leukemia-free survival, or overall survival. Type of disease and disease status at transplant were significant risk factors for leukemia-free survival and overall survival at one year and for transplant-related mortality and relapse at two years. Patients' general health and degree of tissue-type match between recipient and donor were also significant at two years for nearly all outcomes.
American Society of Hematology
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The use of stem cells in regenerative medicine may also be detrimental for health
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NIH launches 2009 H1N1 influenza vaccine trials in HIV-infected pregnant women
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Private umbilical cord banking not cost-effective, UCSF research shows
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Case Western Reserve researchers discover the key to malaria susceptibility in children
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Exposure to phthalates may be a risk factor for low birth weight in infants
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Umbilical Cord Stem Cell Therapy: The Gift of Healing from Healthy Newborns by Anthony G. Payne (Author), David Steenblock (Author) We are standing at the threshold of a new and exciting medical era-an era of regeneration, rejuvenation, and renewal in which stems cells will set the stage for healing and in some cases, the restoration of injured, diseased, and debilitated tissues and organ. While stem cell therapy is still in its infancy, the field is rich with promise. The debate over the use of embryonic stem cells and the questionable effectiveness of adult stem cells have led many scientists and clinicians to concentrate their energies on umbilical-cord-derived stem cells from healthy newborn babies. While these cells are technically classifed as "adult stem cells," they appear to have greater restorative and regenerative potential than stem cells derived from adult tissues due to their young age. Human... |
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ABC News Nightline Your Child's Umbilical Cord If you could derive medical benefits by harvesting the blood from a freshly discarded umbilical cord, it's hard to think of any ethical reason why you shouldn't do so. As it is, about 3.5 million umbilical chords are thrown into the trash every year. Since that cord blood, as it's known, is rich in blood-forming stem cells, which can then be used in transplantation instead of bone marrow, saving it, storing it would seem to make eminently good sense. Indeed, there are already several thriving businesses that have grown up around that very premise. For a couple of thousand dollars or so, the companies will collect the blood from your baby's umbilical cord. And for about $100 a year, they'll store it in a refrigerated container. Then, should the baby or any immediate member of the... |
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Rambo First Blood Green Cord Wrapped Num. Sign. Edition by Master Cutlery ATTRIBUTES Blade Detail: Plain Edge Blade Length (inches): 9.00 Blade Material: Stainless Carry System: Leather Sheath Handle Material: Cord Wrapped Overall Length (inches): 14.00 Special Features: Numbered and Signature Survival Kit in Handle |
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Microlife AD-120 AC Adapter by Microlife The Microlife AC Adapter Model #AD-120 is a convenient alternative to batteries for Microlife brand automatic and semi-automatic blood pressure monitors. It fits standard electrical outlets and features a convenient long cord. Input: 120VAC 60HZ 15V, Output: 6VDC 600MA. Not compatible with Microlife Model #3MQ1 (use AC Adapter AD-1024A). |
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Thermo Scientific CryoMed CryoPlus and Cryo Series Racks and Holders;10 Place Cord Blood Rack by Thermo Scientific Cord Blood Freezer Rack;Thermo Scientific; CryoMed; 10-place; For use with all CryoMed Freezer Models | |
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coupon for cord blood registery during pregnancy value $250 Discount Code# MMEDS by CBR, Cord Blood Registery A SPECIAL GIFT FOR YOU FROM A CBR MOM ALL YOU HAVE TO DO IS GO TO CORDBLOOD.COM THE OFFICIAL CBR WEBSITE ENTER THIS CODE: MMEDS WHEN YOU REGISTER OR CALL 1-888-CORD BLOOD AND GIVE THEM THIS DISCOUNT CODE: MMEDS AND THEY WILL GIVE YOU THE DISCOUNT DIRECTLY AND SEND YOU THE KIT WITH ALL THE INFORMATION THAT YOU WILL NEED. IF YOU DO WANT TO CONTACT ME DIRECTLY PLEASE PLACE YOUR BID AND I CAN SEND YOU ALL THE INFORMATION AND HANDLE YOUR REGISTRATION WITH CBR PERSONALLY WITH NO ADDITIONAL COST PLEASE REMEMBER YOU MUST TAKE THAT KIT WITH YOU TO THE HOSPITAL AT THE TIME OF DELIVERY AND YOU MUST INFORM YOUR DOCTOR IN ADVANCE OF YOUR DECISION TO STORE YOUR CHILDS CORD BLOOD THIS IS A ONCE IN A LIFETIME OPPORTUNITY PLEASE DONT LET IT PASS YOU BY! I HAVE MANY FRIENDS WHO REGRET... |
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John Rambo: First Blood Signature Edition Knife Replica by Hollywood Collectibles Hollywood Collectibles has recreated Rambo's historic knives from the film trilogy that began with First Blood, continued in Rambo: First Blood Part II, and concluded in Rambo III! The First Blood Signature Edition knife measures 14" in overall length and features a top-quality 420 stainless steel blade with slotted saw teeth, a hollow handle with survival kit, aluminum butt cap with precision compass, and a double screwdriver guard. The Rambo: First Blood Part II Signature Edition knife features a matte finish stainless steel blade, center slotted saw teeth, Phillips and standard screwdriver points, stainless guard with lashing holes, hollow handle wrapped in heavy nylon cord with waterproof O-Rings and survival kits and non-magnetic aluminum butt-cap with precision compass. Offered for... |
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