研究論文

Clinical Applications of Blood-Derived and Marrow-Derived Stem Cells for Nonmalignant Diseases

MSC
Author
Master
Date
2015-07-08 03:33
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Clinical Applications of Blood-Derived and Marrow-Derived Stem Cells for Nonmalignant Diseases(2008)



Source : www.jama.com
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, non hematologic 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 sub study 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 non myeloablative,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 17reports 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.

STEM CELLS ARE UNDIFFERENTIated cells that through replication have the capability of both self-renewal and differentiation into mature specialized cells. In broad terms, there are 2 types of stem cells, embryonic stem cells and adult stem cells. Human embryonic stem cells are isolated from a 50- to 150-cell, 4- to 5-dayold postfertilization blastocyst. Embryonic stem cells generate every specialized cell in the human body and, while capable of indefinite ex vivo proliferation, exist only transiently in vivo (during embryogenesis).
Adult stem cells are located in tissues throughout the body and function as a reservoir to replace damaged or aging cells. Under physiologic conditions, adult stem cells are traditionally thought to be restricted in their differentiation to cell lineages of the organ system in which they are located.
Embryonic stem cells have great promise and versatility but, compared with adult stem cells, are currently difficult to control due to their tendency to form tumors containing all types of tissue, ie, teratomas. Embryonic stem cell biology has been associated with ethical controversy, and feeder cell–free and xenogeneic-free culture methods approved by the US Food and Drug Administration are still being perfected. In contrast, adult stem cells normally behave well without formation of tumors and follow traditional lineagespecific differentiation patterns, fulfilling their physiologic homologous function of replacing normal turnover, aging, or damaged tissues. For these reasons, this review will be confined to adult stem cells.

©2008 American Medical Association. All rights reserved.
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