Transdifferentiation
Neil Neumann
Wednesday, 31 October 2007 17:01 UTC
What do people in this group think about an adult stem’s proposed ability to transdifferentiate (eg hematopoietic stem cell contributing to muscle lineages)?
-Neil
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There is a fair amount of evidence, but transdifferentiation is a hard event to nail down. You really have to track it on a single-cell level to make a definitive conclusion, and the tools aren’t available for this just yet. For example, the membrane dyes such as CellTracker can be picked up and internalized by existing cells. So there’s always a question whether you’ve got differentiation or simply selection of lineage-restricted progenitors, but I’ve seen LacZ-marked MSCs costain with Troponin, which strongly suggests transdifferentiation.
The current consensus is that transdifferentiation does occur, within a limited range. For example, bone marrow derived cells such as MSCs are believed by pretty much everyone studying them to differentiate into bone, fat and cartilage(and different groups accept different levels of evidence for transdiff into neurons, muscle, pancreatic beta cells, etc). Elaine Fuchs has done a pretty detailed study of the hair follicle, tracing stem cells from their niche in the bulge to the various types of cells that make up a hair follicle.
The things is, though, that most people working on Adult stem cells are fairly clinically-focused. They’re interested in finding out if the cells can be used for cellular therapy, and whether the reparative effect occurs by transdifferentiation or possibly transient paracrine effects on the engrafted tissue is only of secondary interest to them.
In the end, there’s a lot of basic definitions of terms that need to be settled before the question can really be answered. For example, if a cell is expressing alpha-fetoprotein or insulin, does that mean it’s a hepatocyte or islet cell, or some other kind of cell which has taken on some hepatocyte or pancreatic cell function? If you read the literature on MSCs, you’ll be frustrated by the apparently many and varied different kinds of cells all called MSCs.
My PI is promoting the use of a standardized preparation of cells, which I’ve linked to as the group website.
That’s really the basic issue that is being dodged in most adult progenitor cell research right now – what are the criteria for calling a cell a member of any given cell type. The assays used are functional ones, so you can differentiate a culture and compare that culture to another culture, but you never know how many stem cells you started out with, and even putting a portion of a cell sample through an assay using limiting dilutions can’t answer whether the differences in differentiation are due to proliferation of the stem cells prior to differentiation, or greater efficiency of differentiation in the absence of stem cell proliferation. That’s a hard question to answer, and the tools aren’t really available yet. Ideally, we’d be able to do gene expression profiling on many single cells serially, pre and post differentiation, and really nail the answer.
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I have been associated with my uncle DR.B.V.Shenoi who has done work on Lymphocyte transdifferentiation at Kolar gold fields in India.His monograph begins like this.
“If we begin with certanities,we shall end in doubts,but if we begin with doubts we shall end with certanities”-Francis Bacon.He has used Sodium Nitroprusside to stimulate Lymphocytes to other granular cell types.The work may seem crude by present standards yet might shed new light on the process of transdifferentiation.www.ias.ac.in/currsci/aug252004/491.pdf
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The website www.ias.ac.in/currsci/aug252004/491.pdf.The monographs presented way back in 1989 are lectin induced lymphocyte to granulocyte transformation of avian and mammalian lymphocytes invitro,human erytroblast to granulocyte transformation and an interspecies lymphocyte to granulocyte from avian to human types-Qualitive cytomorphological study;Ita implications for medicine.By B.V.Shenoi
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The other monograph is on Cytohistologic evidence for a stemcell role of endothelium in histogenisis.Tissues removed at surgery are grown in fowl plasma lead to homoplastic proliferation and heteroplastic differentiation to epithelial cell types.My uncle died recently in april.Shold anybody find this interesting I shall post reply,and send the monogrphs gratis,I have only a few.
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That’s interesting, Jagesh. Has anyone followed that up will cell surface markers?
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my uncle had used factor8 to identify the endothelium, and flow cytometry to study the lymphocyte fractions.The endothelium as well as the differentiated epithelia carried the factor8 which is specific for endothelium.The flow cytometry was indeed fascinating that the granulocytic transdifferentiation was established.The time taken for this phenomenon was barely 30 minutes,and most of the lymphocytes changed in to granulocytes.This work has been published by an MSC Student for his thesis last year.The factor8 studies have not been published.Also tagging the cells also needs to be done.Being a dermatologist in practice is my handicap.I only wish somebody can look in to this.Jagesh
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The most striking and notable cytomorphologic feature in general,among others is the intial proliferation of elongated spindle shaped endothelial cells in the form of long sprouts and tendrils without a basement membrane arranged in a tandem fashion and in parellel forming closely packed bundles of undifferentiated cells,which subsequently undergo morphological transformation into cells with oval,round or spherical nuclei exhibiting partial epitelial cell characteristics.This is soon followed by cytoplasmic bridging of cells to form sheets of epithelial cells,some exhibitng glandular or tubular structures.
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The concept that the vascular system might be responsible for osteogenisis was put forward in 1763 by Albert von Haller.Keith expressed the view that endothlium,like Trueta who came to the conclusion that osteogenic cells are primarily derived from the vascular endothelium.Rigal found that during osteogenic induction the vessel wall enters the synthetic phase of mitotic cycle. Keith Sir A concerning the origin of osteoblasts.Proc Roy Soc Med 1927:21:301.Trueta J. The role of vessels in osteogenisis.Bone.jt.Surg1963:43-B:402
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Transdifferentiation is exciting stuff that for certain. Non-stem’s cell transforming into different types of cells, or creating other cells is something that we should all be interested in! I have been using sciquest.org to keep updated on new stem cell research and developments. Although there have been some recent breakthroughs in this area I still think much more funding is needed to really crack open this and other related scientific, medical technologies.
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“Nothing would be done at all,if a man waited till he could do so well that no man could find fault with it”-
Cardial Newman.A spectacular finding in our work is finding an interspecies transdifferentiation of fowl thymic lymphocytes into human type well substantiated by peroxidase stained smears, when stimulated by euphorbia lectin.The sequential morphological events in transforming lymphocytes, the foremost being cell aggregation,polaristion, meaning the lymphocytes assuming hand-mirror forms exhibiting active mobility,a monocytoid phase in transition,proceeding to final transformation to granulcytes.”vision is the art of seeing th invisible”-Jonathan Swift.
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