Research on CB Transplantation

• 1. Is it better to collect cord blood before or after delivery of the placenta?
• 2. What is the optimum cord blood collection method, gravity drip versus syringe?
• 3. What is the optimum cord blood storage container , bags or vials?
• 4. What is the long-term viability of frozen cord blood?
• 5. How long does it take to search for a cord blood donor?
• 6. How long does it take cord blood to engraft in a transplant recipient?
• 7. How does Graft Versus Host Disease (GVHD) from cord blood compare to other sources of stem cells?
• 8. Does cord blood carry a Graft-Versus-Leukemia effect?
• 9. What is the minimum dose of stem cells from cord blood needed for engraftment of a new immune system?
• 10. Can the use of cord blood for adults be enhanced by expanding the number of stem cells in vitro?
• 11. Can the use of cord blood for adults be enhanced by combining multiple, mis-matched, cord blood units?
• 12. What is the maximum degree of patient-donor incompatibility (mismatched HLA types) that can be tolerated in cord blood transplants?
• 13. What is the oldset person who can receive a cord blood transplant?
• 14. How does long-term survival compare among recipients of bone marrow transplants versus cord blood transplants?
• 15. Which poses less risk of passing an inherited disorder, adult bone marrow or infant cord blood?
• 16. What is the probability that a person will require a transplant of autologous stem cells (ie: their own stem cells) over the course of a lifetime?
• 17. Are there more primitive types of stem cells hidden among blood stem cells, awaiting discovery?
• 18. Can cord blood stem cells be used for gene therapy?
• 19. Can cord blood stem cells repair damage to the Central Nervous System?
• 20. Can cord blood stem cells correct inherited metabolic disorders?
• 21. Can cord blood stem cells be used for organ regeneration?
• 22. Are there reports of cord blood "cures" which have dubious validity?

Abstracts for medical research articles on any topic can be found from the on-line search engine of the National Library of Medicine: PubMed.

Answer: This is a close call.

References:

• Solves P, et al. 2003; Bone Marrow Transplant. 2003 Feb;31(4):269-73. In a sample of 569 vaginal deliveries, a larger volume and a higher number of stem cells were harvested from the in utero collection group.
• Lasky, LC, et al. 2002; Transfusion Oct;42(10):1261-7 They say that, in terms of sample volume and cell count, there is "no advantage of either method".
• Surbek, DV, etal. 2000; Am J Obstet Gynecol Jul;183(1):218-21 They prefer in utero collection for cesarean delivery

Example: One bank which collects ex utero has a slide show of the collection process.

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Answer: Studies have shown that pulling the blood out with a syringe tends to draw a bigger sample than simply letting the blood drip by gravity into a bag.

References:

• Bertolini F, et al. (1995) J Hematother Feb;4(1):29-36. "Comparative study of different procedures for the collection and banking of umbilical cord blood."
• Elchalal U, et al. (2000) Am J Obstet Gynecol. Dec;183(6):1587-8. These authors advocate flushing all the blood out with saline, which is a more aggressive method than simply pulling out blood, and is not in routine use.

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There is no clear answer: Existing scientific studies do not show a significant difference between blood storage in bags versus syringes.

A given bank will use only bags or vials, not both, because their freezer is equipped with racks for holding either one or the other. Also, the loading of the racks should be balanced for mechanical and temperature stability.

On the one hand, those banks that use bags like to point out that they are a "closed system", in which the blood does not have to be transfered from one container to another. This lessens the chances of contamination if the transfer is not done with proper sterile technique. Of course, blood labs are not supposed to be hiring employees who don't know how to transfer blood properly.

On the other hand, those banks that use vials like to point out that frozen bags are prone to shattering if they are not handled very carefully. Of course, they should be handled very carefully. 

A bank which uses vials has the option of separating the cord blood into multiple vials. If the sample is stored in multiple portions, then the family has the option of using it one portion at a time, should medical research develop new therapies in which this is desirable. (However, multi-compartment bags can achieve the same purpose)

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(Actually, all the studies of cord blood viability have been done on samples of separated Mono-Nuclear Cells, not whole blood.) Answer: So far, recovery of viable stem cells from cord blood is over 90% at 15 years.

References:

• Kobylka, P., et al. 1998, Transplantation, 65(9):1275-1278.
• Mugishima, H., et al. 1999, Bone Marrow Transplant, 23(4):395-396.
• Broxmeyer, H. E., et al. 2003 pnas.0237086100
  

Background information: In theory, it should be possible to store cells for millenia at -196 C, the temperature of liquid nitrogen. Below -130 C, no liquid water exists in cells, which prevents biochemical reactions between molecules dissolved in water. At -196 C there is not enough thermal energy in the cell to drive any biochemical reaction. The only degradation that can occur at this temperature is reactions caused by cosmic background radiation. It can be calculated that, at normal terrestrial conditions, it would take about 2000 years before such reactions caused a significant amount of damage.

References:

• Mazur P. 1988, Ann NY Acad Sci. 541:514-31. "Stopping biological time. The freezing of living cells"
• Mazur P. 1984, Am J Physiol. 1984 Sep;247(3 Pt 1):C125-42. "Freezing of living cells: mechanisms and implications."
   

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Answer: At least a month less than to find a bone marrow donor. Median time to chose a cord blood unit is 13.5 days (range, 2-387), compared to median time to approve an unrelated bone marrow donor of 49 days (range, 32-293), in a summary of 171 donor searches over the course of a year at the University of Minnesota. The "additional time taken to obtain a BM donor was predominantly due to the additional 30-day interval (range, 10-101 days) required to clear the donor".

Reference:

• Barker, JN et al. (2002) Biology of Blood & Marrow Transplantation vol.8(issue 5):257-260

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Answer: At least a week longer than it takes bone marrow to engraft. Median engraftment times for bone marrow and cord blood are typically 18 and 26 days.

References:

• Rocha, V., et al. (2000) NEJM 342:1846-54
• Wadlow & Porter (2002) Biology of Blood & Marrow Transplantation vol.8(issue 12):637-647

New Answer: Research is underway to speed up engraftment. Expanding the number of stem cells in cord blood (see question 10.) makes it possible to transplant bigger patients, but does not speed up engraftment. In Aug 2004, a research team at led by Hal Broxmeyer at Indiana University School of Medicine (press release) announced that they can speed up engraftment by inhibiting or deleting CD26, an enzyme on the surface of stem cells. The initial publication describes research on mice, but human trials are planned.

Reference:

• Christopherson, KW II et al., 13 Aug 2004 Science 305(5686), 1000-1003. "Modulation of Hematopoietic Stem Cell Homing and Engraftment by CD26"

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Answer: GVHD is less severe with cord blood than with bone marrow. In a study where all patients received an HLA-matched transplant from a sibling, and the results were controlled for age, the relative risk of cord blood versus bone marrow was 0.41 for acute GVHD and 0.35 for chronic GVHD.

The accepted explanation is that cord blood carries much less GVHD than bone marrow because the newborn baby is "immunologically immature" -- ie., the immune system has not had time to be exposed to various foreign bodies and develop reactions against them.

Reference:

• Rocha, V., et al. NEJM 2000;342:1846-54

In late 2003 it was announced that a patient's risk for GVHD is also governed by genetics: those patients who carry the gene "C/C interleukin-10" are 2.6 times more likely to get GVHD after a perfectly matched sibling transplant than patients who carry the A/A genotype.

Reference:

• Lin et al. NEJM 2003; 49(23):2201-10

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Answer: Apparently very little, if any. Graft-versus-Tumor effect is known to be correlated with Graft-Versus-Host Disease (GVHD). Both are mediated by T-cells. While the T-cell content of umbilical cord blood is lower than bone marrow, it is not low enough to be the sole factor explaining the lower incidence of GVHD in cord transplants. Apparently the types of T-cells, their maturity, and their activity also differ. This is a frontier of on-going research.

References:

• Wadlow & Porter (2002) Biology of Blood & Marrow Transplantation vol.8(issue 12):637-647

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Answer: This is the same as asking, "what is the maximum patient size that can be transplanted with a single cord blood collection?" The optimal dose is about 20 million nucleated cells per kilogram of body weight. "patients who received no more than 10 million nucleated cells per kilogram had a 75 percent probability of death, whereas recipients of at least 30 million nucleated cells per kilogram had a 30 percent probability of death."

Reference:

• Editorial by Gluckman, E. NEJM 2001;344:1860

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Answer: Yes. Many biotech companies are developing techniques to rapidly grow stem cells in a laboratory environment. These methods are being used in clinical trials.

Example: Blood & Marrow Transplant Newsletter issue #51 reports on the first adult to survive a cord blood transplant with expanded stem cells. Published by Pecora et al. 2000 Bone Marrow Transplantion 25:797-799.

References:

• MJ Laughlin et al., 2001; NEJM 344(24):1815-22. Retrospective study of 68 adults who received cord blood; 90% engrafted.
• EJ Shpall et al., 2002; Biology of Blood & Marrow Transplantation vol.8:368-376. "Transplantation of Ex Vivo Expanded Cord Blood". Reports on a clinical trial conducted at the U. of Colorado on 25 adults & 12 children with high-risk diagnosis.
• J Jaroscak et al., 2003; Blood 2003 101:5061-67. Phase I trial on 28 patients of conventional UCB transplants augmented by ex vivo-expanded cells.

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Answer: Yes. See the next question.

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Answer: Apparently quite large. Examples:

Several clinical trials presented at the 43rd annual meeting of the American Society of Hematology in Dec. 2001 were transplanting adults with multiple (from 2 to 6) mis-matched cord blood units. Surprisingly, although these patients initially show a mix of HLA types ("chimerism") from the different units, over time most survivors display a single dominant cord blood type.

• Reference: Cord blood transplants: Making do with less by M.D. John Wingard

Report on an adult patient in Britain who recovered after receiving a transplant of 7 cord blood units; one perfect match and 6 mis-matched

• Reference: The Guardian newspaper 7/9/2002

Report on a study at the U. of Minnesota in which 23 patients were transplanted 2000-2003. Each received two partially matched cord blood units (now at 32 patients as of fall 2004). They have not figured out yet how to predict which cord blood unit will dominate in the end!

• Reference: Barker JN, et al. Blood Oct2004; DOI 10.1182/blood-2004-07-2717. "Transplantation of two partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy."

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Answer: Approximately age 70. A study at the University of Minnesota transplanted patients who were not eligible for high-dose chemotherapy, either due to age, co-existing medical problems, or previous treatment. The median age was 49 (range from 19 to 69). They received reduced conditioning chemo, also known as a "mini transplant". Sustained engraftment was 89% overall, and 98% in patients who had ablative chemotherapy (enough to wipe out bone marrow) within three months prior to transplant.

Reference:

• Wagner J. and Barker J. (Oct2004) Biol Blood Marrow Transplant. 10(10):733-4. "Umbilical cord blood transplantation after a non-myeloablative therapy in high risk adults."

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Answer: They are comparable. Among pediatric patients, the overall survival rates are comparable for the two transplant types, but the causes of death differ with each. Among cord blood transplants, the most common cause of death was complications during the long wait for engraftment. Among bone marrow transplants, more patients died of severe Graft-Versus-Host Disease. Despite the fact that cord blood seems to lack graft-versus-tumor activity, cord blood transplants were not associated with higher rates of patient relapse.

Reference:

• Wadlow & Porter (2002) Biology of Blood & Marrow Transplantation vol.8(issue 12):637-647 "Umbilical cord blood transplantation: where do we stand?"

Among adult patients, perfectly matched bone marrow is preferable to cord blood, but mis-matched bone marrow and mis-matched cord blood yield comparable outcome. In Nov 2004, two studies were published in the New England Journal of Medicine which announced that cord blood transplants are suitable for adults who lack a perfectly matched HLA donor.

References:

• Laughlin MJ, et al. Nov2004; NEJM 351(22):2265-75. "Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia." This USA study found no difference between outcomes of cord blood transplants (150 patients) with 1 or 2 HLA mis-matches versus bone marrow transplants (83 patients) with one HLA mis-match. Please note, a perfect bone marrow match (367 patients) is still better than cord blood for adult patients.
• Rocha V, et al. Nov2004; NEJM 351:2276-2285. "Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukemia." This European study compared 98 cord blood transplants (98 patients, 94% of them mis-matched) with bone marrow transplants (584 patients, all matched). There were no significant differences in occurance of chronic GVHD, transplantation-related mortality, relapse rate, and leukemia-free survival.

More in-depth answer: Cord blood stem cells may hold an advantage in telomere length. Telomeres are like molecular caps that tie off the ends of chromosones. As cells replicate, their telomeres get shorter. Literally, telomere shortening is the aging process at the cellular level. For example, when Dolly the sheep was cloned from a six year old cell, she was born with shortened telomeres, as if she was already six years old. Some researchers have suggested that telomere shortening in hematopoietic stem cell transplantation (ex: giving an old person's stem cells to a young patient) is a potential mechanism for late graft failure.

References:

• Awaya, N. et al. (2002) Biology of Blood & Marrow Transplantation vol.8(issue 11):597-600

Another in-depth answer: Cord blood is more effective in repopulating the stem cell "reservoir". Although it is well known that cord bood takes longer than bone marrow to engraft after transplant, a recent study indicates that in the long run (after one year) the cord blood does a better job of re-populating the body's reservoir of blood stem cells. The cause for both of these effects is that the stem cells in cord blood would rather multiply than differentiate into more evolved blood cells.

References:

• Francesco Frassoni et al. 2003 Blood First Edition Paper: prepublished online 4/10/2003 DOI 10.1182/blood-2003-03-0720

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Answer: This is a toss-up. More and more diseases are now recognized to have a genetic basis. We have always known that some diseases are passed by inheritence. Now we also recognize that some genetic mutations confer a greater predisposition to disease. For example, the "Philadelphia chromosome (translocation)" is associated with a predisposition to developing leukemia at some point in life. Many of these inherited predispositions do not manifest until adulthood. Plus, if the donor has one of these predispositions, some of the drugs that transplant patients take could trigger a malignancy in the donor cells.

On the one hand, older donors are better because they have more medical history to rule out inherited mutations. On the other hand, older donors are worse because they are more likely to have an acquired mutation, from exposure to disease or chemicals, etc. At this time, it is not clear whether older or younger donors are better.

It is possible to test donor cells for inherited mutations, which would be present in every cell. But with hundreds of known mutations, only a limited number can be screened with a reasonable amount of blood.

References:

• McMilin, K., 4/1/2002 Transfusion vol.42(issue 4):495

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Answer: Approximately 1 in 400 up to age 70, or 0.25%

Reference:

• Nietfeld, J.J., and Verter, F. 2Oct2004 presentation at Tufts U. Medicine ICBS conference
  or PowerPoint slides (808 KB)

Previous references:

• 1 in 2,703 up to age 20: F.L. Johnson, 1997; J Ped Hem Onc 19(3): 183-186 (probability based on diagnosis rates and treatment modalities)
• 1 in 20,000 up to age 20: G.J. Annas, 1999; NEJM 340: 1521-1524. (probability is stated without proof)
• 1 in 10,000 to 1 in 200,000 over a lifetime: R.M. Kline, April 2001; Sci Amer 4: 30-37. (probability is stated without proof)

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Answer: Almost certainly. Examples:

Press Release 1 Nov 2000 from StemCells, Inc. (Nasdaq: STEM) "First Identification of Purified Blood Stem Cells as a Source of Mature Liver Cells; Published in Nature Medicine

Nature 20 June 2002 vol.417. Catherine Verfaillie of the U. Minnesota Medical School and her team claim to have extracted "multipotent adult progenitor cells" from adult bone marrow which can turn into every type of tissue in the body, just like embryonic stem cells.

Press release 19 July 2004 from Viacell and NETCORD announces the first demonstration that neonatal "unrestricted somatic stem cells" (USSCs) can be robustly expanded in vitro (in the lab) to very large numbers and can differentiate, in vivo (in living humans), into a number of tissue types and take on the properties and specific functions of the cells in those tissues: blood, bone, cartilage, heart, liver, and nerve cells.

Reference:

• "A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential"; published in the peer-reviewed article by Kogler et al., Journal of Experimental Medicine (JEM) 2004 Jul 19;200(2):123-35.

In May 2005, the biotechnology company BioE, based in St. Paul, MN, becomes the first company to commercially market multi-potent stem cells extracted from cord blood. Their "Multi-Lineage Progenitor Cells™ (MLPCs™)" have differentiated into tissues representative of neural stem cells, nerve cells, liver/pancreas precursors, skeletal muscle, fat cells, bone cells and blood vessels.

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Answer: Yes. Traditionally, patients with severe hereditary disorders of the immune system were given a stem cell transplant to replace the defective gene. This is kind of like fixing a broken transmission by replacing the whole car. Plus, while the patient's hereditary disorder may be fixed, there are new medical problems associated with a transplant that is not a perfect match.

The more sophisticated approach is to transplant the patient's own stem cells after they have been genetically engineered to fix the defective gene. The genetic engineering is done with a virus. The patient's own cord blood is an ideal source of matching stem cells.

Example: Transplants of genetically engineered cord blood have been successfully used to cure some forms of "bubble boy syndrome", or SCID. Initially, the SCID results were touted as the first success story of gene therapy. Unfortunately, this clinical trial was halted in 2003 when two of the children subsequently developed leukemia. It is not clear at present if the leukemia was triggered by the gene insertion process, or if the SCID patients simply had a greater predilection towards leukemia than the population at large.

References:

• Parkman R, et al. 2000, Annual Rev Med 51:33-47 (ADA-SCID)
• Salima Hacein-Bey-Abina, et al. 2002, NEJM 346:1185-1193 (X-linked SCID)
• Antoine C, et al. 2003, Lancet 361(9357):541-2. "Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: report of the European experience 1968-99."
• Sara M. Mariani 2003, Highlights of the 2003 meeting of the American Association of Immunologists, reported by Medscape 6/3/03

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Answer: Probably. In the lab, stem cells from umbilical cord blood can be induced to develop into nerve cells. When neural cells derived from blood stem cells are transplanted into lab mice, the cells have been shown to survive and function. The hope is that, eventually, there will be established procedures to infuse cord blood into human beings, get the stem cells to turn into nerve cells, and have those nerve cells function in the body to fix the patient's problem.

Disorders of the Central Nervous System (CNS) which might be treated with stem cells:

• degenerative diseases: Parkinson's, Alzheimer's, Multiple Sclerosis
• traumatic damage: post-stroke, spinal cord injuries
• hereditary diseases: Huntington's, Leukodystrophies

The page on Diseases Treated by Blood Stem Cells sorts CNS diseases according to whether they are in a very experimental stage of research or are undergoing clinical trials with human patients. Also, the News Page chronicles some miraculous cures claimed with cord blood infusions (for example, see the entries for Dec 2004).

Research Report: Multiple Sclerosis
Stem cell transplants as a therapy for Multiple Sclerosis have been in clinical trial for several years. These trials are using autologous stem cells from the patient, not cord blood. The transplants seem to have slowed the progression of MS in some patients. But the transplant itself carries a significant risk of mortality, about 10%, and thus was only tested in patients with severe MS who were not responding to other treatments.

References:

• press release 4/16/2002 from the American Academy of Neurology annual meeting.
• Nash RA, et al. 5/22/2003 Blood. A team led by George Kraft of the Fred Hutchinson Cancer Research Center, Seattle, WA, tried autologous stem cell transplants on 26 MS patients, followed over a period of three years.
• Fassas A, et al. 8/2002, J Neurol. 249(8):1088-97. Researchers in Italy and Greece performed a retrospective study of stem cell transplants in 85 MS patients.

Research Report: Amyotrophic Lateral Sclerosis (ALS; or "Lou Gehrig's Disease")
Cord blood transplants as a therapy for ALS are currently in clinical trial. The ALS Therapy Development Foundation issued a review of "Human Umbilical Cord Blood Therapies in ALS" in Dec. 2002, followed by an update on cord blood; subsequently the Muscular Dystrophy Association opened a clinical trial of cord blood transplant for ALS in 2003.

Research Report: Alzheimer's Disease
In July 2003, the NIH granted $1.4 million over 5 years for research on the conversion of stem cells into neurons. The grant went to the CSO of NewNeural, a privately-held biotech company founded by Dr. Kiminobu Sugaya and two other colleagues; their research works with stem cells from adult bone marrow. In Feb 2005, the University of Central Florida issued a press release that Sugaya's lab, together with colleagues the University of Illinois at Chicago, are the first to demonstrate improved memory in adult animals after transplanting neural stem cells into their brains. The NewNeural team achieved the results by treating bone marrow cells in laboratory cultures with bromodeoxyuridine, a compound that becomes part of DNA, and made adult human stem cells more likely to develop as brain cells after they were implanted in adult rat brains.

Research Report: Stroke
While the news media are reporting miraculous cures that supposedly occured in far-away lands, in the published medical literature the use of stem cells to treat stroke has not advanced beyond mice.

Reference:

• Borlongan CV, Hadman M, Sanberg CD, Sanberg PR 2004: Stroke. 35(10):2385-9
  "Central nervous system entry of peripherally injected umbilical cord blood cells is not required for neuroprotection in stroke." In this study, cord blood stem cells were given intravenously to mice after stroke, together with a drug to help the cells permeate the blood-brain-barrier. Stroke size was dramatically reduced by 40%, and long-term disability was also significantly reduced.

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Answer: Probably. Some hereditary disorders cause the metabolism to gradually destroy the nervous system, as well as damage other organs. One class of hereditary disorders is leukodystrophies, in which the cells sheathing nerves are improperly developed or maintained, and gradually break down. Another class of hereditary disorders is storage disorders, in which cells are damaged by the abnormal accumulation of waste products. There are different types of storage disorders: Mucopolysaccharidoses (MPS) Storage Diseases (includes Hurler's Syndrome, Sanfilippo Syndrome) and Lysosomal Storage Diseases (includes Gaucher Disease, Tay-Sachs).

The team lead by Joanne Kurtzberg, M.D., at Duke University, is conducting trials of cord blood transplants in very young children with various inherited disorders. So far, they have presented successful results with Sanfilippo Syndrome, Hurler's Syndrome, and Krabbe Disease.

References:

• Duke University press release Jan 2004, also presented at American Society of Hematology Dec 2003 meeting
• Medscape CME on Hurler's Syndrome, based on
• Staba, SL, et al., N Engl J Med. 2004; 350:1960-1969. "Cord-blood transplants from unrelated donors in patients with Hurler's syndrome."
• Escolar ML, et al., N Engl J Med. 2005; 352(20):2124-6. "Transplantation of umbilical-cord blood in babies with infantile Krabbe's disease."

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Answers: There are so many YES/MAYBE answers that they have to be enumerated.

Cellular Cardiomyoplasty
This is a new field of medicine in which stem cell transplantation is used to repair or regenerate damaged heart muscle. Animal studies have shown that stem cells from bone marrow can survive in dead heart muscle and improve its ability to contract. As of late 2002, this technique has entered phase I clinical trials with human beings.

In the trials, the stem cells are injected into the perimeter of the dead muscle. Most studies have harvested the stem cells from bone marrow, although blood stem cells have also been harvested by apheresis of the circulating bloodstream. The bone marrow is sometimes injected fresh, or sometimes filtered to increase the percentage of stem cells. So far, many different approachs are being attempted because this field is still in its infancy.

The first molecular evidence that stem cells from cord blood can repair heart damage in transplant patients was announced by researchers at Duke University in Feb 2004.

References:

• Stamm, C. et al. (4Jan2003) The Lancet 361:45-46
• Tse, H.-F. et al. (4Jan2003) The Lancet 361:47-49
• News reports about study results presented at the American Heart Association meeting: CNN 10Nov2003
• Press releases from the American Heart Association: AHA 11Nov2003
• Press release from Duke University, to be presented at the International Association of Bone Marrow Transplantation Research meeting 12-17Feb2004 in Orlando, FL: IBMTR Feb2004
• Web page from the FDA’s BRMAC (Biological Response Modifiers Advisory Committee), dated 15Mar2004, on the clinical development of cellular products to be used in the treatment of heart diseases.
• Wollert, KC et al. (10Jul2004) The Lancet 364(9429):141-8.
  "Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial"
• Botta, R. et al. (Sep2004) FASEB J. 18(12):1392-4.
  "Heart infarct in NOD-SCID mice: therapeutic vasculogenesis by transplantation of human CD34+ cells and low dose CD34+KDR+ cells."

Vascular regeneration
Several research groups are experimenting with cord blood as a raw material for tissue engineering, particularly the development of vascular grafts. There are also reports that diabetic patients with severe damage to peripheral blood vessels (this is called "lower limb ischemia") have been saved from amputation by the infusion of blood stem cells from their own bone marrow.

References:

• Schmidt D et al. (Dec.2004) Ann Thorac Surg. 78(6):2094-8. "Umbilical cord blood derived endothelial progenitor cells for tissue engineering of vascular grafts."
• Press release 6Oct2003 from Aastrom Biosciences announcing SBIR grant from NIH for Phase I Clinical Trial to develop stem cell treatment for in vivo animal model of limb ischemia.
• Yamamoto et al. (Dec2004) Arterioscler Thromb Vasc Biol. 24(12):192-196. "Molecular evaluation of endothelial progenitor cells in patients with ischemic limbs: therapeutic effect by stem cell transplantation."

Skin growth for wound repair
References:

• Valbonesi M, et al. (2004) Transfusion and Apheresis Science. 30:153-156. "Cord blood (CB) stem cells for wound repair. Preliminary report of 2 cases."

Kidney repair
Several research groups (example: U. of Queensland, Australia) are working to take stem cells from bone marrow and elicit them to grow into renal cells. Moreover, donor stem cells are being infused in combination with kidney transplants to reduce patient need for immunosuppressive drugs that prevent organ rejection.

Liver repair
References:

• Kakinuma S, et al., Stem Cells. 2003;21(2):217-27. "Human umbilical cord blood as a source of transplantable hepatic progenitor cells."

Diabetes / Pancreas
References:

• Ende N, Chen R, Reddi AS. (Aug2004) Biochemical and Biophysical Research Communications. 321(1):168-71. "Transplantation of human umbilical cord blood cells improves glycemia and glomerular hypertrophy in type 2 diabetic mice."
• Ende N, Chen R, Reddi AS. (Dec2004) Biochemical and Biophysical Research Communications. 325(3):665-9. "Effect of human umbilical cord blood cells on glycemia and insulitis in type 1 diabetic mice."

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Answer: YES. The most miraculous cures always seem to come from parts of the world with little medical oversight. Does this mean the USA FDA is too strict or the claims are bogus? Judge each case for yourself. Examples:

Using a child's own cord blood to treat cancer:
The advertising of private cord blood banks seems to suggest that cord blood can be used to treat the baby if s/he develops cancer. This is extremely unlikely. While adult cancers result from acquired cell mutations, there is evidence that many pediatric cancers arise from inborn genetic abnormalities. In that case, it is not safe to treat the child with (autologous) transplants of their own stem cells.

Sample reference:

• Backtracking leukemia to birth , Rowley, Janet D. 1998 Nature Medicine vol.4(2) 150-151

There are, however, exceptions to this rule: The 2002 report of the European Group for Blood and Marrow Transplantation recognizes autologous transplant as standard practice for children with high risk AML in first remission. See Table 2 of Urbano-Ispizua A, et al., 2002 Bone Marrow Transplantation vol.29(8) 639-646.

The Parkinson's cure in India:
Dr. Dinesh Garg achieved reknown in the United States by founding a private cord blood bank, LifeCord USA, which turned out to be a mailing address with no lab. (No relation to other banks named "Lifecord" in Gainesville, FL, Graz, Austria, and Korea.) After that scam was exposed, he fled the country for India, where the Times of India reported 12Sept2001 that Dr. Garg has "cured" Parkinson's patients with cord blood transplants. The report claims that brain cells "derived by modification of discarded umbilical cord blood stem cells" were infused into the cerebrospinal fluid while cooling the brain and spinal cord. The Indian news reports have been repeated uncritically by the American media.

Dr. Garg has returned to the United States and his supporters seek funding to conduct a clinical trial of his procedure here.

Steenblock Research Institute (SRI):
SRI claims that Dr. Fernando Ramirez DelRio in Tijuana, Mexico, has given "pure" cord blood stem cells, administered with no prior immunosuppression, to treat seven children with cerebal palsy. (Editorial notes: 1. Scientists have no marker for stem cells, so it is impossible to separate "pure" stem cells. 2. Without immune suppression, the patient's body will reject any kind of stem cells.) They report that one child was cured of blindness (Nov2004). By contrast, in medical academia, the most advanced study at Harvard which used stem cells to restore vision was performed in MICE (reported 18Nov2004).

Criticism of SRI: The consumer organization QuackWatch lists Steenblock under Questionable "Research" Entities (see their 9 guidelines) and provides links to regulatory actions [1, 2] against Steenblock.

Defense from SRI: Dr. Anthony G. Payne has created a page refuting Quackwatch which insists that SRI merely reports on therapies performed with umbilical cord cells by foreign-based physicians.
Follow-up article on the boy who was blind (June2005).

Central American clinics which thrive on Russian abortions:
Alan Zarembo of the LA Times reports that several clinics in Central America trace their roots to the Institute for Problems of Cryobiology and Cryomedicine in Kharkov, Ukraine, directed by Dr. Valentin Grischenko. Since 1972, this institute has experimented with medical treatments using cells from aborted fetuses. Based on the institute's work, in the early 1990s, a group of Ukrainian researchers started a Kiev company called EmCell, charging $25,000 per treatment.

In the late 1990's, Malibu psychiatrist William Rader founded a company named Medra to offer similar fetal cell treatments. Initially based in the Bahamas, Rader now operates a clinic in the Dominican Republic which offers fetal stem-cell treatments for $30,000.

The Barbados Nation Newspaper reported 14Nov2004 that the Barbados Institute provides regenerative therapy to patients under the treatment protocols developed by Dr. Valentin Grischenko. The article states that the CEO of Barbados Institute is Barnett Suskind, the embryonic cells come from fetuses aborted in the Ukraine, and the cost is (US)$25,000 per person.

The Shady Side of Embryonic Stem Cell Therapy
The consumer website QuackWatch, operated by Stephen Barrett, M.D., has devoted an entire page to unregulated clinics which are claiming miraculous cures with stem cells. Some of these clinics are using umbilical cord blood.

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