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Sweet Success for ASCs in Bone Regeneration

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Review of “Local Application of Isogenic Adipose-Derived Stem Cells Restores Bone Healing Capacity in a Type 2 Diabetes Model” from Stem Cells Translational Medicine by Stuart P. Atkinson

While bone healing is usually efficient in healthy patients, conditions such as type 2 diabetes can impair this process [1], leading to more complications in an already at-risk population. Researchers from the laboratory of Björn Behr (Ruhr University Bochum, Germany) hypothesized that the implantation of isogenic adipose-derived stem cells (ASCs) could promote bone healing and improve vascularization of the affected zone, and thereby aid bone regeneration in diabetic patients. Their new study in Stem Cells Translational Medicine employs a mouse model of type 2 diabetes (Lepbrdb-/-) and isogenic mASCs to demonstrate that this treatment strategy may be highly useful for human patients [2]. Does this represent a sweet success for ASCs?

Initial in vitro studies demonstrated that ASCs-derived from the fat pads of diabetic (Lepbrdb-/-) mice (DB-ASCs) actually exhibited increased osteogenic potential compared to wild type ASCs (WT-ASCs). Therefore, the authors assessed their in vivo bone-regenerative capacity by transplantation into a unicortical tibial defect in a mouse model (See figure – DB-ASC marked in green). 

GFP-labelled ASCs successfully colonized the bone defects in diabetic mice, and both DB- and WT-ASCs mediated an important increase in angiogenesis near the injury site. However, they only observed significantly enhanced osteogenesis, proliferation, and terminal differentiation of DB-ASCs and not WT-ASCs. The improvement observed with DB-ASC treatment correlated to a significant increase in bone regeneration in diabetic animals, but not in WT animals, which the authors link to the potent paracrine influence of the transplanted ASCs.

So how are ASCs promoting bone healing in the context of type 2 diabetes? The authors suggest that ASCs may rectify impaired endothelial progenitor cells and endothelial cell migration [3] and thereby promote angiogenesis. Additionally, the hyperglycemic condition caused by type 2 diabetes may elevate the proliferative and differentiative capacity of ASCs [4], thereby promoting osteogenesis. Given the ease of collection of ASCs and their relative (and unfortunate) abundance, could the application of ASCs represent “sweet success” for bone regeneration in diabetic patients?

References

  1. Retzepi M and Donos N The effect of diabetes mellitus on osseous healing. Clin Oral Implants Res 2010;21:673-681.
  2. Wallner C, Abraham S, Wagner JM, et al. Local Application of Isogenic Adipose-Derived Stem Cells Restores Bone Healing Capacity in a Type 2 Diabetes Model. Stem Cells Transl Med 2016;5:836-844.
  3. Wallner C, Schira J, Wagner JM, et al. Application of VEGFA and FGF-9 enhances angiogenesis, osteogenesis and bone remodeling in type 2 diabetic long bone regeneration. PLoS One 2015;10:e0118823.
  4. Garcia-Jimenez C, Garcia-Martinez JM, Chocarro-Calvo A, et al. A new link between diabetes and cancer: enhanced WNT/beta-catenin signaling by high glucose. J Mol Endocrinol 2014;52:R51-66.