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Profiles and Perspectives
Stem Cells Trans Med 2014; 3:560-563; first published on March 28, 2014; doi:10.5966/sctm.2013-0180
Stem Cells Trans Med 2014; 3:405-415; first published on March 5, 2014; doi:10.5966/sctm.2012-0159
The author proposes a novel mechanism to explain why leukemia stem cells (LSCs) are refractory to tyrosine kinase inhibitors in which Bcr-Abl signaling is fundamentally different in LSCs compared with nonstem leukemia cells and LSCs rely on kinase-independent Bcr-Abl signaling for survival.
Stem Cells Trans Med 2014; 3:135-140; first published on December 26, 2013; doi:10.5966/sctm.2013-0134
Hypoxia-inducible factors (HIFs) are oxygen-sensitive transcription factors regulated by oxygen-dependent prolyl hydroxylase domain (PHD) enzymes and are key to cell adaptation to low oxygen. The hematopoietic stem cell (HSC) niche in the bone marrow is highly heterogeneous in terms of microvasculature and thus oxygen concentration. The importance of hypoxia and HIFs in the hematopoietic environment is becoming increasingly recognized. Many small compounds that inhibit PHDs have been developed, enabling HIFs to be pharmacologically stabilized in an oxygen-independent manner. The use of PHD inhibitors for therapeutic intervention in hematopoiesis is being increasingly investigated. PHD inhibitors are well established to increase erythropoietin production to correct anemia in hemodialysis patients. Pharmacological stabilization of HIF-1α protein with PHD inhibitors is also emerging as an important regulator of HSC proliferation and self-renewal. Administration of PHD inhibitors increases quiescence and decreases proliferation of HSCs in the bone marrow in vivo, thereby protecting them from high doses of irradiation and accelerating hematological recovery. Recent findings also show that stabilization of HIF-1α increases mobilization of HSCs in response to granulocyte colony-stimulating factor and plerixafor, suggesting that PHD inhibitors could be useful agents to increase mobilization success in patients requiring transplantation. These findings highlight the importance of the hypoxia-sensing pathway and HIFs in clinical hematology
Stem Cells Trans Med 2014; 3:2-6; first published on November 29, 2013; doi:10.5966/sctm.2013-0104
Cell therapy for heart disease began clinically more than a decade ago. Since then, numerous trials have been performed, but the studies have been underpowered, focusing primarily on low-risk patients with a recent myocardial infarction. Many data have accumulated on surrogate endpoints such as ejection fraction, but few clinical conclusions can be drawn from such studies. We argue here that the time is right for targeting larger and/or higher-risk populations for whom there is some expectation of being able to influence mortality or rehospitalization.
Stem Cells Trans Med 2013; 2:727-730; first published on August 29, 2013; doi:10.5966/sctm.2013-0099
This article presents a draft of Points to Consider when using human somatic cells obtained from research donors to derive and subsequently distribute induced pluripotent stem cells (iPSCs), with the goal of initiating a deliberative process to develop consensus for such use.
Stem Cells Trans Med 2013; 2:638-640; first published on August 9, 2013; doi:10.5966/sctm.2013-0040
There is a large, poorly regulated international market of putative stem cell products, and demand for these products is growing. Very few stem cell biologics have passed regulatory scrutiny, and authorities in many countries have begun to step up their enforcement activities to protect patients and the integrity of health care markets.
Stem Cells Trans Med 2013; 2:635-637; first published on July 24, 2013;doi:10.5966/sctm.2012-0089
HIV infection has been cured by a hematopoietic cell transplantation (HCT) using peripheral blood stem cells from an adult donor homozygous for CCR5-Δ32, but this approach cannot be readily generalized because of the low prevalence of the CCR5-Δ32 allele and the need for a very close human leukocyte antigen (HLA) match between adult donors and recipients. Cord blood (CB) transplantation does not require as stringent an HLA match between donor and recipient, and therefore cryopreserved homozygous CCR5-Δ32 CB units provide a feasible means to potentially cure reasonable numbers of patients who are infected with HIV. CB units are being screened to develop an inventory of cryopreserved homozygous CCR5-Δ32 units available for HCT.
Stem Cells Trans Med 2013; 2:553-557; first published on July 1, 2013;doi:10.5966/sctm.2013-0011
Repair in the peripheral nervous system (PNS) is a complex process that requires the active de-differentiation of Schwann cells to an immature repair state following injury; this de-differentiation is dependent upon the activity of the p38 and ERK1/2 mitogen-activated protein kinases, as well as the transcription factor cJun. Understanding the mechanisms of repair raises the possibility of both boosting repair after PNS trauma and even, possibly, blocking the inappropriate demyelination seen in some disorders of the peripheral nervous system.
Stem Cells Trans Med 2013; 2:401-408; first published on May 15, 2013; doi:10.5966/sctm.2012-0185
This article examines the pros and cons of using different autologous stem cell sources for abdominal aortic aneurysm (AAA) therapy, the requirements they must fulfill to provide therapeutic benefit, and the current progress toward characterizing the cells' ability to synthesize elastin, assemble elastic matrix structures, and influence the regenerative potential of diseased vascular cell types. The article also provides a detailed perspective on the limitations, uncertainties, and challenges that will need to be overcome or circumvented to translate current strategies for stem cell use into clinically viable AAA therapies.
Stem Cells Trans Med 2013; 2:325-327; first published on April 18, 2013; doi:10.5966/sctm.2013-0057
The goals of New York's Empire State Stem Cell Board (ESSCB) are to ignite the growth of a thriving stem cell research community within New York, to stimulate the local economy, and to provide support for efforts to discover treatments and cures for debilitating diseases and injuries. Dr. Nirav R. Shah, New York Commissioner of Health and chair of the ESSCB, shares its history and its approach to research.