Stem cells for diabetes: 2 types better than one

This is an finding, 'a long time in coming'. It reminds me of the days when we were trying to induce purified hematopoietic stem cells to divide and eventually found that not 1, not two, but three specific growth factors were required to shift the HSC into cell division.
Also, a remarkable recent study was reported in JAMA 2007 Apr 11;297(14):1568-76:"Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus." by Voltarelli J.

Stephen Bartelmez PhD
CSO & Founder
BetaStem Therapeutics Inc.
Stem Cell Therapy for Diabetes and Cancer
665 3rd Street, Suite 250
San Francisco, CA 94107-1926
206-427-0350

Well I guess it is always better to replicate nature when we are trying to do things in vitro and as you know, nature doesnt usually only use one cytokine.

I wonder what role the nervous system plays in all of this. For example, the bone marrow, thymus, and spleen are all innervated.

Christine...I agree. Your point rarely breaks the surface in the scientific community, but has been a major point for decades. Innervation within the marrow must pay a significant role that we all have missed. What about the pancreas...perhaps more is evident there. Someday, someone will figure this anatomy out.

Stephen Bartelmez PhD
CSO, President & Founder
BetaStem Therapeutics Inc.
Stem Cell Therapy for Diabetes and Cancer
665 3rd Street, Suite 250
San Francisco, CA 94107-1926
206-427-0350

c this

Cell. 2006 Dec 15;127(6):1123-35. Links
Comment in:
Cell. 2006 Dec 15;127(6):1097-9.
TRPV1+ sensory neurons control beta cell stress and islet inflammation in autoimmune diabetes.Razavi R, Chan Y, Afifiyan FN, Liu XJ, Wan X, Yantha J, Tsui H, Tang L, Tsai S, Santamaria P, Driver JP, Serreze D, Salter MW, Dosch HM.
Neurosciences and Mental Health Program, The Hospital for Sick Children, Research Institute, University of Toronto, Toronto, ON, Canada, M5G 1X8.

In type 1 diabetes, T cell-mediated death of pancreatic beta cells produces insulin deficiency. However, what attracts or restricts broadly autoreactive lymphocyte pools to the pancreas remains unclear. We report that TRPV1 pancreatic sensory neurons control islet inflammation and insulin resistance. Eliminating these neurons in diabetes-prone NOD mice prevents insulitis and diabetes, despite systemic persistence of pathogenic T cell pools. Insulin resistance and beta cell stress of prediabetic NOD mice are prevented when TRPV1 neurons are eliminated. TRPV1, localized to the Idd4.1 diabetes-risk locus, is a hypofunctional mutant, mediating depressed neurogenic inflammation. Delivering the neuropeptide substance P by intra-arterial injection into the NOD pancreas reverses abnormal insulin resistance, insulitis, and diabetes for weeks. Concordantly, insulin sensitivity is enhanced in trpv1(-/-) mice, whereas insulitis/diabetes-resistant NODxB6Idd4-congenic mice, carrying wild-type TRPV1, show restored TRPV1 function and insulin sensitivity. Our data uncover a fundamental role for insulin-responsive TRPV1 sensory neurons in beta cell function and diabetes pathoetiology.

This is too much on the edge for me. So Stemcellgood, what this paper is saying is that those vanilloid receptor neurons are somehow implicated in the initial wave of dendritic cells that infiltrate the pancrease in the non-obese diabetic mouse?

The paper also talks about insulin resistance, a neural basis for insulin resistance, sensitivity would be very interesting.

Dr. Bartelmez, it seems like your a diabetes guy, what do you make of this paper?

Christine, I wouldn't describe myself as a diabetes guy...I am just am fascinated with the complexity of this disorder (I am a hematopoietic stem cell, MSC, huES kind of guy). Anyway, this Cell paper is very intriguing and the mechanism may be important. BUT, does this anatomy and physiology exist in humans ?? Mice and men are not so similar sometimes. HOWEVER, these two recent studies also add to the complexity: 1) Cell Metabolism, Vol 6, 320-328, 03 October 2007 "Inhibition of PKC- epsilon Improves Glucose-Stimulated Insulin Secretion and Reduces Insulin Clearance" by Carsten Schmitz-Peiffer et al and 2) Cell, 2007 August 10; 130(3): 456–469, "Endocrine regulation of energy metabolism by the skeleton" by Na Kyung Lee et al. Regulation of sugar levels is proving to be complicated.

Dear Dr Bartelmez,

I know that this sounds really out there but I have to share it. Once I met a man from the middle east who was blindfolded and put in front of a firing squad. The firing squad shot the gun but not at him.

Subsequently he developed diabetes ! Would this have anything to do with nerve activation?

Well, Stemcellgood, I too love stories. And a paper or story does not make fact. In biology especially, it is always difficult to know what is fact as "proven" by humans. I like reproducibility best: can I predict what will happen ?? Hey I like aspirin, it always has the same effect on me...but do I really know the mechanism...