Diabetes Irreversibly Depletes Bone Marrow-Derived Mesenchymal Progenitor Cell Subpopulations
- Michael Januszyk, MD*,1,2,
- Michael Sorkin, MD*,1,
- Jason P. Glotzbach, MD1,
- Ivan N. Vial, MD1,
- Zeshaan Maan, MD1,
- Robert C. Rennert, BA1,
- Dominik Duscher, MD1,
- Hariharan Thangarajah, MD1,
- Michael T. Longaker, MD1,
- Atul J. Butte, MD PhD3 and
- Geoffrey C. Gurtner, MD1⇑
- 1Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA
- 2Program in Biomedical Informatics, Stanford University School of Medicine, Stanford, CA
- 3Division of Systems Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA
- Corresponding Author: Geoffrey C. Gurtner, E-mail:
Diabetic vascular pathology is largely attributable to impairments in tissue recovery from hypoxia. Circulating progenitor cells have been postulated to play a role in ischemic recovery and deficiencies in these cells have been well described in diabetic patients. Here, we examine bone marrow-derived mesenchymal progenitor cells (BM-MPCs) that have previously been shown to be important for new blood vessel formation, and demonstrate significant deficits in the context of diabetes. Further, we determine that this dysfunction is attributable to intrinsic defects in diabetic BM-MPCs that are not correctable by restoring glucose homeostasis. We identify two transcriptionally distinct subpopulations that are selectively depleted by both type 1 and type 2 diabetes, and these subpopulations have pro-vasculogenic expression profiles, suggesting that they are vascular progenitor cells. These results suggest that the clinically observed deficits in progenitor cells may be attributable to selective and irreversible depletion of progenitor cell subsets in patients with diabetes.
* These authors contributed equally to this work.
- Received September 5, 2013.
- Accepted April 9, 2014.
- © 2014 by the American Diabetes Association.
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