Abstract
Objectives:
Wound healing and angiogenesis are impaired in patients with diabetes and peripheral vascular disease. We developed a novel treatment by systemic administration of mesenchymal stem cells (MSC) coated with nanocarrier composed of adhesion molecule -nanoparticle complex (AMNC). AMNC-MSC significantly enhanced wound healing and angiogenesis, in wild type and diabetic mice. AMNC-MSC targeted homing is specific to the injured tissue and superior to BSA (control)-NC coating or uncoated MSC. We now investigate the biosafety profile of the AMNC-MSC.
Method:
1x 10
6
HUVEC were coated with AMNC. Cytotoxicity of AMNC was evaluated by trypan blue. Cell apoptosis was analyzed by flow cytometry using FITC-Annexin-V and propidium iodide. 12-14 week-old C57BL6 mice (N=15) underwent 6mm full thickness dorsal dermal wounding and then assigned to 3 IV treatment groups: (i) 1x 10
6
AMNC-MSC, (ii) 1x 10
6
MSC and (iii) equivalent volume saline (No Treatment (NT); (n=5/group). Day 8 post-wounding and treatment, comprehensive metabolic panel, complete blood count and urinalysis were obtained.
Result:
AMNC-MSC had no cytotoxicity to HUVEC. Blood tests and urinalysis revealed that the hematological, hepatic, renal and pancreatic functions were normal in all groups. Hyperglycemia was observed among all groups at comparable level (p=0.136), likely a stress response. All other blood/urine parameters were within normal, in all groups.
Conclusion:
AMNC-MSC has no observed cytotoxicity to human endothelial cells,
in vitro
. Intravenous administration of AMNC-MSC does not cause metabolic or hematologic toxicity, in mice. We demonstrate initial biosafety of novel nanocarrier-targeted MSC therapy which holds promise in pro-angiogenic and pro-healing regenerative medicine.