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Presenter: Paolo , Bianco, Rome, Italy
Authors: Paolo Bianco
What is known worldwide by the biological misnomer “Mesenchymal Stem Cells” is in essence what was know for many years before as the Bone Marrow Stromal Cells, long postulated to include a genuine stem cell for the different tissues that together comprise the skeleton. The concept of a stem cell for skeletal tissues has recently found direct experimental proof in humans and mice, and was significantly developed beyond the orginal formulation. It is now apparent that skeletal stem cells (MSCs) are perivascular cells of skeletal origin, provide the unique niche for hematopoiesis and hematopoietic stem cells, and are bona fide stem cells inasmuch as capable not only of multipotency (as classically known) but of self-renewal in vivo. Over the years, the original concept has been impressivley distorted without the distortions ever being backed by the necesary experimental evidence. The isolation of human pluripotent embryonic cells in culture initially casted on the field the ungrounded suggestion that “MSCs” could be an adult version of pluripotent cells, a notion now dispelled by experimental evidence. The suggestion had two implications: 1) that MSCs could be “doctored” to differentiation ex vivo, like pluripotent cells can, and 2) that they could be used within a true regenerative paradigm to restore the anatomy and function of non-skeletal and even non-mesodermal tissues (such as heart or brain). This view later gave way to the alternative view that restoration of such tissues could be ascribed not to a genuine regenerative event, but to vaguely defined “trophic” “antiinflammatory”, immune modulatory effects. While none of these has either been conclusively proven as a biological function of MSCs, or shown to be clinically relevant, over 300 studies around the planet attempt to verify such effects in clinical studies that lack either the rationale or the statistical power needed. Most of these studies are driven, directly or indirectly, by commercial interests, which are slowly replacing, in the field of MSCs, science as the source of science itself and of medical advances. The implications of misread biology and medicine are manifold, and do include the flourishing of a new kind of stem cell quackery that is rapidly spreading worldwide and undermining drug regulation. Meanwhile, major progress in understanding the biology of “MSCs” are being made, which would suggest novel but strikingly different directions for medical developments, which remain disregarded as a result of the heavily commercial climate established in the field.
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