Interesting question. I am interested, since I work with stem cells, but I am also a diabetic subject. Could you specify your stem cells? Do you mean hematopoietic stem cells or mesenchymal stem cells, and do you have any idea whether these stem cells have a hyperglycaemic state? And maybe also good to specify your DM type I or II?

No. I do not think. The influence, in this situation is pretty transient .

Are you referring to adipose tissue MSCs?

Dear Elisa,

As for my knowledge, there are reports of functional impairment observed in progenitor cells (particularly EPCs) obtained from diabetic subjects Vs. normal human subjects (Ref: http://circ.ahajournals.org/content/106/22/2781.short) however, this is a primary culture scenario. i.e., culture from 7-21 days (even before first passage).

but cells after several passages may lose the glycaemic memory. But I think this problem can be circumvented by culturing them in media supplemented with 30 mM glucose, which is the cell culture equivalent for hyperglycaemia.

Hope this information is useful

please refer to this review, it may help.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3059410/.

Thank you all for your answers. I'm referring to type I diabetes and to cardiac stem cells, that possess the features of mesenchymal stem cells.

I'm going to study some functional characteristics of cardiac stem cells in type I diabetes.

Hi Elisa

Frist of all, you must specify the type of stem cells you have isolated. Secondly, I think it depends upon how long these cells were subjected to hyperglycemia. In addition, stem cells functions are controlled by both intrinsic and extrinsic regulatory cues. The regenerative activity of stem cells also appears to be tightly linked to metabolism, and alterations in metabolic state can directly influence the activity of these stem cells. Finally, i want to ask if these cells were allowed to grow in normal growing media (in vitro), is it possible to behave normally, this need experiment.

Dear Elisa:

My gut feeling to your question is: "NO!". Diabetes is probably the result of some unknown factor that kills differentiated beta cells in the pancreas. Some evidence exists that in that diabetic pancreas, minus beta cells, there still exists adult pancreatic stem cells in the pancreas. While in the developing fetus, these adult pancreatic stem cells can differentiate into all pancreatic cell types, in the adult organisms, the surviving adult pancreatic stem cells either can't differentiate or if they do, the differentiated beta cells are still subject to the same original external killing factor. This factor in non-genetic-predisposed organisms has to be external to its own genomic DNA.

That's my interpretation.

Jim Trosko, Ph.D.

I would like to add to Jim interpretations that there is a defect in the regulatory T cells of diabetic patients which suppose to control autoreactive T cells which are responsible for beta cell killing. MSCs are an upstream immunoregulators of T regulatory cells and there may be there is a defect also in these MSCs. A scientist in my lab is investigating this and our preliminary data support such phenomena.

Well, I personally believe that if the "diabetic" state is caused by a genetic mutation or not (as is the case in the mouse model, though no concrete evidence of this has been elucidated in humans). If there is a genetic modification (or potentially even a secondary modification i.e. methylation) then your stem cells may not behave similar to "normal" stem cells and hence retain the diabetic state. If there is no hardwire difference then the cells you isolate will most likely act similarly to normal cardiac stem cells. Regardless, when you do isolate your cells make sure you have the proper controls (i.e. same gender, age and ethnic origin) as many factors can affect the biology of stem cells.

Might it be wise to follow a metabolite profile over time, to see it it changes?

Hi Elisa, have u isolated cardiac stem cells in diabetic mice or human? Have u find different behavior between normal or diabetic stem cells? Have u induced diabetes in mice with streptozotocin? All these questions for the reason why I think it's very different talk about stem cells from mice, where u can only pharmacologically induce a diabetes, or diabetic human condition. However, in my experience if u perform your experiment immediately after extraction u haven't problem but if u what to give there some splits u have to improve the medium with glucose to mimic hyperglicemic conditions.

Good idea Kathleen. Following metabolite profile in normal and hyperglycaemic media should be interesting whatever the result.

Thank you for your answers and suggestions. I isolated human cardiac stem cells from diabetic subjects and cultured them for several passages in basal gucose medium. Now I'd like to know if these cells retain a metabolic memory of diabetic status or not. At the moment I use an in-vitro model of hyperglycemia for my experiments (on cells isolated from healthy patients) but it should be interesting studying stem cells isolated directly from diabetic subjects, for example also from mice (Streptozotocin model).

I remain pleasantly struck for the reason why that you can easily extract cardiac stem cells and that even after different passages these cells maintain both the stemness that the same characteristics of freshly extracted cells. Some years ago, when I'll try to work with these type of cells it was very difficult also define it!!! However when I worked with BM diabetic stem cells, the behaviour of stem cells extracted by diabetic or cultured in a medium mimic diabetic status was not quite the same.