 |
|
Clinical Applications of Blood-Derived and Marrow-Derived Stem Cells for Nonmalignant Diseases
Richard K. Burt, MD;
Yvonne Loh, MD;
William Pearce, MD;
Nirat Beohar, MD;
Walter G. Barr, MD;
Robert Craig, MD;
Yanting Wen, MD;
Jonathan A. Rapp, MD;
John Kessler, MD
JAMA. 2008;299(8):925-936.
Context Stem cell therapy is rapidly developing and has generated excitement and promise as well as confusion and at times contradictory results in the lay and scientific literature. Many types of stem cells show great promise, but clinical application has lagged due to ethical concerns or difficulties in harvesting or safely and efficiently expanding sufficient quantities. In contrast, clinical indications for blood-derived (from peripheral or umbilical cord blood) and bone marrow–derived stem cells, which can be easily and safely harvested, are rapidly increasing.
Objective To summarize new, nonmalignant, nonhematologic clinical indications for use of blood- and bone marrow–derived stem cells.
Evidence Acquisition Search of multiple electronic databases (MEDLINE, EMBASE, Science Citation Index), US Food and Drug Administration [FDA] Drug Site, and National Institutes of Health Web site to identify studies published from January 1997 to December 2007 on use of hematopoietic stem cells (HSCs) in autoimmune, cardiac, or vascular diseases. The search was augmented by hand searching of reference lists in clinical trials, review articles, proceedings booklets, FDA reports, and contact with study authors and device and pharmaceutical companies.
Evidence Synthesis Of 926 reports identified, 323 were examined for feasibility and toxicity, including those with small numbers of patients, interim or substudy reports, and reports on multiple diseases, treatment of relapse, toxicity, mechanism of action, or stem cell mobilization. Another 69 were evaluated for outcomes. For autoimmune diseases, 26 reports representing 854 patients reported treatment-related mortality of less than 1% (2/220 patients) for nonmyeloablative, less than 2% (3/197) for dose-reduced myeloablative, and 13% (13/100) for intense myeloablative regimens, ie, those including total body irradiation or high-dose busulfan. While all trials performed during the inflammatory stage of autoimmune disease suggested that transplantation of HSCs may have a potent disease-remitting effect, remission duration remains unclear, and no randomized trials have been published. For reports involving cardiovascular diseases, including 17 reports involving 1002 patients with acute myocardial infarction, 16 involving 493 patients with chronic coronary artery disease, and 3 meta-analyses, the evidence suggests that stem cell transplantation performed in patients with coronary artery disease may contribute to modest improvement in cardiac function.
Conclusions Stem cells harvested from blood or marrow, whether administered as purified HSCs or mesenchymal stem cells or as an unmanipulated or unpurified product can, under appropriate conditions in select patients, provide disease-ameliorating effects in some autoimmune diseases and cardiovascular disorders. Clinical trials are needed to determine the most appropriate cell type, dose, method, timing of delivery, and adverse effects of adult HSCs for these and other nonmalignant disorders.
Author Affiliations: Divisions of Immunotherapy (Drs Burt, Craig, and Wen), Cardiology (Drs Beohar and Rapp), Rheumatology (Dr Barr), and Gastroenterology (Dr Craig), Department of Medicine; Division of Vascular Surgery, Department of Surgery (Dr Pearce); and Department of Neurology (Dr Kessler), Northwestern University Feinberg School of Medicine, Chicago, Illinois; and Department of Hematology, Singapore General Hospital, Singapore (Dr Loh).
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
RELATED LETTERS
Hematopoietic vs Embryonic Sources for Stem Cell Research
Steven Teitelbaum, Shane Smith, and William Neaves
JAMA. 2008;299(23):2746.
EXTRACT
| FULL TEXT
Hematopoietic vs Embryonic Sources for Stem Cell Research—Reply
Richard Burt, John Kessler, and Yvonne Loh
JAMA. 2008;299(23):2746-2747.
EXTRACT
| FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Route of delivery and baseline left ventricular ejection fraction, key factors of bone-marrow-derived cell therapy for ischaemic heart disease
Brunskill et al.
Eur J Heart Fail 2009;11:887-896.
ABSTRACT
| FULL TEXT
Allogeneic mesenchymal stem cells restore cardiac function in chronic ischemic cardiomyopathy via trilineage differentiating capacity
Quevedo et al.
Proc. Natl. Acad. Sci. USA 2009;106:14022-14027.
ABSTRACT
| FULL TEXT
Platelet MPs obscure some EPC definitions
Yoder
Blood 2009;114:495-496.
FULL TEXT
Cardiac repair and regeneration: the Rubik's cube of cell therapy for heart disease
Boudoulas and Hatzopoulos
DMM 2009;2:344-358.
ABSTRACT
| FULL TEXT
High glucose concentration in cell culture medium does not acutely affect human mesenchymal stem cell growth factor production or proliferation
Weil et al.
Am. J. Physiol. Regul. Integr. Comp. Physiol. 2009;296:R1735-R1743.
ABSTRACT
| FULL TEXT
Heart failure therapy mediated by the trophic activities of bone marrow mesenchymal stem cells: a noninvasive therapeutic regimen
Shabbir et al.
Am. J. Physiol. Heart Circ. Physiol. 2009;296:H1888-H1897.
ABSTRACT
| FULL TEXT
The transcriptome of human CD34+ hematopoietic stem-progenitor cells
Kim et al.
Proc. Natl. Acad. Sci. USA 2009;106:8278-8283.
ABSTRACT
| FULL TEXT
Donor-derived oral squamous cell carcinoma after allogeneic bone marrow transplantation
Janin et al.
Blood 2009;113:1834-1840.
ABSTRACT
| FULL TEXT
Promise of Blood- and Bone Marrow-Derived Stem Cell Transplantation for Functional Cardiac Repair Putting It in Perspective With Existing Therapy.
Reffelmann et al.
J Am Coll Cardiol 2009;53:305-308.
ABSTRACT
| FULL TEXT
Cellular Cardiomyoplasty: What Have We Learned?
Kao et al.
Asian Cardiovasc. Thorac. Ann. 2009;17:89-101.
ABSTRACT
| FULL TEXT
Engineered Antibody Fragments with Infinite Affinity as Reporter Genes for PET Imaging
Wei et al.
JNM 2008;49:1828-1835.
ABSTRACT
| FULL TEXT
Assessing Identity, Phenotype, and Fate of Endothelial Progenitor Cells
Hirschi et al.
Arterioscler. Thromb. Vasc. Bio. 2008;28:1584-1595.
FULL TEXT
Hematopoietic vs Embryonic Sources for Stem Cell Research
Teitelbaum et al.
JAMA 2008;299:2746-2746.
FULL TEXT
Review: Endothelial progenitor cells: markers of vascular reparative capacity
Povsic and Goldschmidt-Clermont
Ther Adv Cardiovasc Dis 2008;2:199-213.
ABSTRACT
|
