Returns of the Living Dead
Therapeutic Action of Irradiated and Mitotically Inactivated Embryonic Stem Cells
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- cardiovascular disease
- cardiovascular physiology
- cardiovascular science
- ischemic heart disease
- stem cells
From the time of their initial isolation, scientists have been fascinated by one particular characteristic of pluripotent stem cells: their ability to differentiate into specific cell types. Initially, this property was exploited to explore the changes in gene expression that accompany cell fate choices, and a vast amount of knowledge was added to the developmental biology literature, based both on in vitro studies and the generation of mice with specific alterations in crucial loci. With the advent of human embryonic stem cells (ESCs), an additional possibility arose: the chance that these cells might be the source of a new type of therapy, one in which absent or diseased cells were replaced by healthy versions derived from human ESCs. Cardiovascular disease presented an appealing target; the shortage of donor hearts, coupled with the tantalizing possibility of generating unlimited supplies of new myocytes, attracted a great deal of attention.
Article, see p 1286
Of course, there were always other possible candidate cells to be used in this type of therapy. Skeletal myoblasts,1 which are readily obtainable from both allogeneic and autologous sources, as well as cells isolated from the bone marrow,2 bone marrow stroma,3 and other tissue sources,4 were evaluated as possible therapeutic cells. In many cases, these cells were isolated and injected into various types of preclinical models of heart damage with the hope that something about the damaged heart environment would trigger a fundamental change in the nature of the input cells. In fact, in many cases, the injected cells quickly vanished from the injected animals, likely because of immune rejection or the simple stress of transplantation. The observed impermanence of these transplanted cells created a puzzle: why did so many of these cells actually improve heart function …