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Medical Journals on Stem Cells

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The Likelihood of Hematopoietic Stem Cell Transplantation (HCT) in the United States:
Implications
for Umbilical Cord Blood Storage.

HCT effectively treats a variety of malignant diseases. Availability of suitable grafts limits application in some cases, prompting the establishment of banks to store umbilical cord blood for later personal or family use. The likelihood of utilizing stored cells depends, in part, on the likelihood of developing a condition for which HCT is indicated. This study estimates the latter likelihood based on data for current HCT use as reported to the CIBMTR from 2001 through 2003. First, age-related incidences of HCT were calculated; then, using the cumulative incidence function, we calculated the lifetime likelihood under two scenarios. In scenario 1, we calculated the likelihood of receiving an autologous HCT by age, in decades, from birth to 70 years. In scenario 2, we calculated the likelihood of being a candidate for either an autologous or an allogeneic HCT. This likelihood was derived from the number of HLA-identical sibling HCTs multiplied by three (to account for patients considered acceptable candidates but lacking an HLA-matched sibling donor) in addition to the number of autologous HCT. The number of HCT performed represented fewer than 20% of the malignant diagnoses most commonly treated with HCT, according to Surveillance, Epidemiology and End Results (SEER) data. After the second decade of life, the age-related incidences of HCT under both scenarios steadily increased with age. The cumulative incidences for scenario 1 ranged from 0.02% (at age 20) to 0.23% (at age 70); for scenario 2 they ranged from 0.06% (at age 20) to 0.46% (at age 70) (Figure). Given the current indications for HCT, the lifetime likelihood of undergoing an autologous HCT or being a candidate for HCT is about 1 in 400 and 1 in 200, respectively. How closely these estimates correspond to the likelihood that a stored cord blood unit is used depends upon several conditions including a) sufficient number of stem cells; b) satisfactory stem cell quality after the storage period; and, c) relative attractiveness, in particular clinical situations, of cord blood cells compared to other graft sources (e.g. peripheral blood or bone marrow).
SOURCE:
Blood (ASH Annual Meeting Abstracts) 2005 106: Abstract 1330  http://abstracts.hematologylibrary.org

 

Isolation of multipotent mesenchymal stem cells from umbilical cord blood

Oscar K. Lee, Tom K. Kuo, Wei-Ming Chen, Kuan-Der Lee, Shie-Liang Hsieh, and Tain-Hsiung Chen

From the Department of Orthopaedics and Traumatology, Veterans General Hospital-Taipei, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan; Cancer Research Division, National Health Research Institute, Taipei, Taiwan; and Department of Immunology, National Yang-Ming University, Taipei, Taiwan.

It is well accepted that umbilical cord blood has been a source for hematopoietic stem cells. However, controversy exists as to whether cord blood can serve as a source of mesenchymal stem cells, which can differentiate into cells of different connective tissue lineages such as bone, cartilage, and fat, and little success has been reported in the literature about the isolation of such cells from cord blood. Here we report a novel method to obtain single cell-derived, clonally expanded mesenchymal stem cells that are of multilineage differentiation potential by negative immunoselection and limiting dilution. The immunophenotype of these clonally expanded cells is consistent with that reported for bone marrow mesenchymal stem cells. Under appropriate induction conditions, these cells can differentiate into bone, cartilage, and fat. Surprisingly, these cells were also able to differentiate into neuroglial- and hepatocyte-like cells under appropriate induction conditions and, thus, these cells may be more than mesenchymal stem cells as evidenced by their ability to differentiate into cell types of all 3 germ layers. In conclusion, umbilical cord blood does contain mesenchymal stem cells and should not be regarded as medical waste. It can serve as an alternative source of mesenchymal stem cells to bone marrow.

SOURCE: BLOOD, 1 March 2004, Vol 103, No. 5, pp.1669-1678
http://abstracts.hematologylibrary.org

 

Stem Cell Therapy for Autism
ThomasEIchim1, FabioSolano2, EduardoGlenn2, FrankMorales2, LeonardSmith2, GeorgeZabrecky3 and NeilHRiordan*1,4

Autism spectrum disorders (ASD) are a group of neuro developmental conditions whose incidence is reaching epidemic proportions, afflicting approximately 1 in 166 children. Autistic disorder, or autism is the most common form of ASD. Although several neuro physiological alterations have been associated with autism, immune abnormalities and neural hypoperfusion appear to be broadly consistent. These appear to be causative since correlation of altered inflammatory responses, and  hypoperfusion with symptology is reported. Mesenchymal stem cells (MSC) are in late phases of clinical development for treatment of graft versus host disease and Crohn's Disease, two conditionsof immune dysregulation. Cord blood CD34+ cells are known to be potent angiogenic stimulators, having demonstrated positive effects in not only peripheral ischemia, but also in models of cerebralischemia. Additionally, anecdotal clinical cases have reported responses in autistic children receiving cord blood CD34+ cells. We propose the combined use of MSC and cord bloodCD34+cells may be useful in the treatment of autism.

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Address: 1Medistem Laboratories Inc, Tempe, Arizona, USA, 2Institute for Cellular Medicine, San Jose, Costa Rica, 3Americas Medical Center, Ridgefield, Connecticut, USA and 42027 E. Cedar Street Suite 102 Tempe, AZ 85281, USAEmail: ThomasEIchim-thomas.ichim@gmail.com; FabioSolano-doctorsolano@gmail.com; EduardoGlenn-edglenn@yahoo.com; FrankMorales-DrFrank59@aol.com; LeonardSmith-lsmithmd@gmail.com; GeorgeZabrecky-doctorgpz@aol.com; NeilHRiordan*-riordan@medisteminc.com

 

Freezing of living cells: mechanisms and implications
P. Mazur

“Cells can endure storage at low temperatures such as--196 degrees C for centuries. ….The only reactions that can occur in frozen aqueous systems at -196
degrees C are photophysical events such as the formation of free radicals and the production of breaks in macromolecules as a direct result of "hits" by background ionizing radiation or cosmic rays (96). ……… Because terrestrial background radiation is some 0.1 rad/yr, it ought to require some 2,000-4,000 yr at -196 degrees C to kill that fraction of a population of typical mammalian cells.
Needless to say, direct experimental confirmation of this prediction is lacking, but there is no confirmed case of cell death ascribable to storage at -196 degrees C for some 2-15 yr and none even when cells are expose to levels of ionizing radiation some 100 times background for up to 5 yr (48). Furthermore, there is no evidence that storage at -196 degrees C results in the accumulation of chromosomal or genetic changes (6).  Stability for centuries or millennia requires temperatures below -130 degrees C.  Many cells stored above ~-80 degrees C are not stable, probably because traces of unfrozen solution still exist (54).  They will die at rates ranging from several percent per hour to several percent per year depending on the temperature, the species and type of cell, and the composition of the medium in which they are frozen (52)."

References:
96.  Rice, F. O.  History of radical trapping.  In:  Formation and Trapping of Free Radicals, edited by A. M. Bass and H. P. Broida.  New York: Academic, 1960, p. 7.
19.  Elkind, M. M., and G. F. Whitmore.  The Radiobiology of Cultured
Mammalian Cells.  New York:  Gordon and Breach, 1967.
48.  Lyon, M. F., P. Glenister, and D. G. Whittingham.  Long term viability of embryos stored under irradiation.  In:  Frozen Storage of Laboratory Animals, edited by G. H. Zeilmaker.  Stuttgart, FRG:  Fischer Verlag, 1981, p. 139-147.
6.   Ashwood-Smith, M. J., and G. B. Friedmann.  Lethal and chromosomal effects of freezing, thawing, storage time, and X-irradiation on mammalian cells preserved at -196 degrees in dimethyl sulfoxide.  Cryobiology 16: 132-140, 1979.
54.  Mazur, P. Cryobiology: the freezing of biological systems.  Science
168:  939-949, 1970.
52.  Mazur, P. Physical and chemical basis of injury in single-celled
microorganisms subjected to freezing and thawing.  In:  Cryobiology, edited by H. T. Meryman.  London:  Academic, 1966, chapt. 6, p. 213-315.

Am J Physiol Cell Physiol 247: C125-C142, 1984; 0363-6143/84

 

AJP - Cell Physiology, Vol 247, Issue 3 125-C142, Copyright © 1984 by American Physiological Society

Submitted by: Dr. Dayong Gao, Lifebank Medical Scientific Advisory Board Member.

 

Cord Blood Banking for Potential Future Transplantation
In recent years, umbilical cord blood, which contains a rich source of hematopoietic stem and progenitor cells, has been used successfully as an alternative allogeneic donor source to treat a variety of pediatric genetic, hematologic, immunologic, and oncologic disorders. Because there is diminished risk of graft-versus-host disease after transplantation of cord stem cells using matched related donors, the use of less-than-completely matched HLA cord blood stem cells may incur less risk of graft-versus-host disease than mismatched cells from either a related or unrelated "walking" donor, although this remains to be proven. Gene-therapy research involving modification of autologous cord blood stem cells for the treatment of childhood genetic disorders, although experimental at the present time, may prove to be of value. These scientific advances have resulted in the establishment of not-for-profit and for-profit cord blood–banking programs for allogeneic and autologous cord blood transplantation. Many issues confront institutions that wish to establish or participate in such programs. Parents often seek information from their physicians about this new biotechnology option. This document is intended to provide information to guide physicians in responding to parents’ questions about cord blood donation and banking and the types and quality of cord blood banks. Provided also are recommendations about appropriate ethical and operational standards, including informed consent policies, financial disclosures, and conflict-of-interest policies for physicians, institutions, and organizations that operate or have a relationship with cord blood–banking programs.
SOURCE:  PEDIATRICS Vol. 119 No. 1 January 2007, pp. 165-170 (doi:10.1542/peds.2006-2901)  Read full Version

Knowledge and attitudes of pregnant women with regard to collection, testing and banking of cord blood stem cells
Umbilical cord blood is used as a source of hematopoietic stem cells for bone marrow transplantation in the treatment of malignant and nonmalignant disease. We sought to examine pregnant women's knowledge and attitudes regarding cord blood banking, as their support is crucial to the success of cord blood transplant programs.
SOURCE: Canadian Medical Association Journal (CMAJ) March 18, 2003; 168 (6)

Umbilical Cord Matrix, A Rich New Stem Cell Source, Study Shows
The cushioning material or matrix within the umbilical cord known as Wharton's jelly is a rich and readily available source of primitive stem cells, according to findings by a research team at Kansas State University.
SOURCE: Science Daily Magazine. 2003-01-22

Researchers Revive Human Cord Blood that Had Been Frozen for 15 years
Researchers at the Indiana University School of Medicine said Monday that human cord blood frozen in 1985 and 1986 was able to grow in laboratory cultures with the same fresh vigor as fresh cord blood.
SOURCE: Associated Press. 2002-12-30

Hematopoietic Stem-Cell Transplants Using Umbilical Cord Blood
SOURCE: Eliane Gluckman, M.D. New England Journal of Medicine, Vol.344, No.24: June 24, 2001.

Hematopoietic Engraftment and Survival in Adult Recipients of Umbilical-Cord Blood from Unrelated Donors
SOURCE: New England Journal of Medicine, Vol. 344: 1815-1822, No. 24: June 14, 2001.

HOXB4 Overexpression Mediates Very Rapid Stem Cell Regeneration and Competitive Hematopoietic Repopulation
SOURCE: Jennifer Antonchuk, Guy Sauvageau, Keith Humphries. Experimental Hematology 29(9):1125-34. (2001).

Graft-Versus-Host Disease in Children Who Have Received a Cord-Blood or Bone Marrow Transplant from an HLA-Identical Sibling
SOURCE: New England Journal of Medicine, Vol. 342: 1846-1854, No. 25: June 22, 2000.

Outcomes among 562 Recipients of Placental-Blood Transplants from Unrelated Donors
SOURCE: New England Journal of Medicine, Vol. 339: 1565-1577, No. 22: November 26, 1998.

High Efficiency Recovery of Hematopoietic Progenitor Cells with Extensive Proliferative and Ex Vivo Expansion Activity and of Hematopoietic Stem Cells with NOD/SCID Mouse Repopulating Ability from Human Cord Blood Storage frozen for 15 years.
SOURCE: Blood Vol. 98 (Supplement 1) pg 183a; Abstract # 768. [Abstract]

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