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Quality-Quantity Control Culture Boosts the Wound Healing Ability of Diabetic EPCs

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Review of “Quality-quantity control culture enhances vasculogenesis and wound healing efficacy of human diabetic peripheral blood CD34+ cells” from STEM CELLS Translational Medicine by Stuart P. Atkinson

Diabetic patients suffer from poor wound healing due, in part, to a decline in the overall number and function of endogenous human endothelial progenitor cells (EPCs) [1]. As a possible remedy for this problem, researchers from the laboratory of Rica Tanaka (Juntendo University School of Medicine, Tokyo, Japan) recently reported on a serum-free quality-quantity control culture (QQc) system with the ability to return lost functionality to murine diabetic EPCs [2]. 

Now, the team returns with a new STEM CELLS Translational Medicine article in which they describe how their QQc culture approach can boost the vasculogenic and tissue regeneration properties of human diabetic EPCs and improve wound healing in a mouse model [3].

In brief, the QQc ex vivo suspension culture employed culture of CD34+ EPCs [4] from the peripheral blood of diabetic patients in StemSpan™ Serum-Free Expansion Medium (SFEM) supplemented with VEGF, IL‐6, Flt3‐ligand, thrombopoietin, and SCF for seven days. As they hoped, QQc culture increased diabetic CD34+ EPC number, restored lost in vitro differentiation ability/functionality, and promoted the expression of angiogenesis-related and wound-healing genes.

Moving in vivo, the authors compared cell functionality pre- and post- QQc culture following transplantation into the wounds of healthy nude mice and streptozotocin-induced diabetic mice. Excitingly, QQc culture-treated diabetic CD34+ EPCs significantly accelerated wound closure, re-epithelialization, and angiogenesis in both model mice when compared to control untreated mice. The improvements observed in QQc culture-treated cells correlated with enhanced differentiation, direct vasculogenesis, the creation of a more anti-inflammatory environment, and the increased expression of various angiogenic factors and wound-healing genes

The authors propose QQc as an effective means to overcome the inherent limitations of low cell number and low functionality related to autologous cell therapy in diabetic patients, while they also highlight QQc culture’s clinical applicability to a range of diseases, including diabetes, myocardial ischemia, cerebral infarction, and peripheral arterial diseases. However, the authors also note the need to explore the underlying mechanisms behind QQc culture-mediated improvements that could facilitate the optimized design of effective therapeutic modalities.

For more on how quantity-quality control culture can boost the wound healing ability of endothelial progenitor cells from diabetic patients, stay tuned to the Stem Cells Portal!

References

  1. Jarajapu YPR and Grant MB, The Promise of Cell-Based Therapies for Diabetic Complications. Challenges and Solutions 2010;106:854-869.
  2. Tanaka R, Vaynrub M, Masuda H, et al., Quality-Control Culture System Restores Diabetic Endothelial Progenitor Cell Vasculogenesis and Accelerates Wound Closure. Diabetes 2013;62:3207-3217.
  3. Tanaka R, Masuda H, Fujimura S, et al., Quality‐Quantity Control Culture Enhances Vasculogenesis and Wound Healing Efficacy of Human Diabetic Peripheral Blood CD34+ Cells. STEM CELLS Translational Medicine 2018;7:428-438.
  4. Yang J, Ii M, Kamei N, et al., CD34+ Cells Represent Highly Functional Endothelial Progenitor Cells in Murine Bone Marrow. PLOS ONE 2011;6:e20219.