Engineered human vascularized constructs accelerate diabetic wound healing.
Stem cell-based therapy is emerging as a promising approach for chronic diabetic wounds, but strategies for optimizing both cellular differentiation and delivery remain as major obstacles. Here, we study bioengineered vascularized constructs as a therapeutic modality for diabetic wound healing. We developed a wound model in immunodeficient rodent and treated it with engineered vascularized constructs from endothelial progenitors or early vascular cells-derived from human induced pluripotent stem cells (hiPSCs) reprogrammed either from healthy donor or type-1 diabetic patient. We found that all vascularized constructs expedited wound closure and reperfusion, with endothelial progenitor constructs having the earliest maximum closure rate followed closely by healthy and diabetic hiPSC-derivative constructs. This was accompanied by rapid granulation layer formation and regression in all vascularized construct groups. Macrophage infiltration into the hydrogel matrix occurred during early stages of healing, seeming to facilitate rapid neovascularization of the wound that could then better persist in the vascularized constructs. Blood perfusion of the human vasculature could be detected after three days, indicating rapid integration with the host vasculature. Overall, we propose a potential therapeutic strategy using allograft or autologous vascularized constructs to treat type-1 diabetic wounds. This approach highlights the unprecedented prospects of designing patient-specific stem cell therapy.
Department of Chemical and Biomolecular Engineering, Johns Hopkins Physical Sciences - Oncology Center and Institute for NanoBioTechnology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
Yu-I
YI
Shen
Department of Ophthalmology, Johns Hopkins School of Medicine, 400 North Broadway, Baltimore, MD 21287, USA.
Hongkwan
H
Cho
Department of Chemical and Biomolecular Engineering, Johns Hopkins Physical Sciences - Oncology Center and Institute for NanoBioTechnology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA; Department of Biomedical Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
Arianne E
AE
Papa
Department of Chemical and Biomolecular Engineering, Johns Hopkins Physical Sciences - Oncology Center and Institute for NanoBioTechnology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA; Department of Biomedical Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
Jacqueline A
JA
Burke
Department of Chemical and Biomolecular Engineering, Johns Hopkins Physical Sciences - Oncology Center and Institute for NanoBioTechnology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
Xin Yi
XY
Chan
Department of Ophthalmology, Johns Hopkins School of Medicine, 400 North Broadway, Baltimore, MD 21287, USA.
Elia J
EJ
Duh
Department of Chemical and Biomolecular Engineering, Johns Hopkins Physical Sciences - Oncology Center and Institute for NanoBioTechnology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA; Department of Materials Science and Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA. Electronic address: gerecht@jhu.edu.
Sharon
S
Gerecht
D000818:Animals; D002460:Cell Line; D048909:Diabetes Complications / Q000628:therapy*; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology / Q000637:transplantation*; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000637:transplantation*; D008819:Mice, Nude; D018919:Neovascularization, Physiologic; D033581:Stem Cell Transplantation / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry*; D014945:Wound Healing
D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006820:Hyaluronic Acid
Hyaluronan; Hydrogel; Induced pluripotent stem cell; Type 1 diabetes; Wound healing