Safety profile and long-term engraftment of human CD31 + blood progenitors in bone tissue engineering
| Autor: | Rina Elimelech, Hadar Zigdon-Giladi, Gal Michaeli-Geller, Utai Rudich, Eli E. Machtei |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
CD31 Cancer Research Pathology medicine.medical_specialty Angiogenesis Immunology Calvaria Biology Regenerative medicine 03 medical and health sciences 0302 clinical medicine medicine Immunology and Allergy Progenitor cell Bone regeneration Genetics (clinical) Transplantation Cell Biology 030104 developmental biology medicine.anatomical_structure Oncology 030217 neurology & neurosurgery Blood vessel |
| Zdroj: | Cytotherapy. 19:895-908 |
| ISSN: | 1465-3249 |
| Popis: | Background Endothelial progenitor cells (EPCs) participate in angiogenesis and induce favorable micro-environments for tissue regeneration. The efficacy of EPCs in regenerative medicine is extensively studied; however, their safety profile remains unknown. Therefore, our aims were to evaluate the safety profile of human peripheral blood–derived EPCs (hEPCs) and to assess the long-term efficacy of hEPCs in bone tissue engineering. Methods hEPCs were isolated from peripheral blood, cultured and characterized. β tricalcium phosphate scaffold (βTCP, control) or 10 6 hEPCs loaded onto βTCP were transplanted in a nude rat calvaria model. New bone formation and blood vessel density were analyzed using histomorphometry and micro-computed tomography (CT). Safety of hEPCs using karyotype analysis, tumorigenecity and biodistribution to target organs was evaluated. Results On the cellular level, hEPCs retained their karyotype during cell expansion (seven passages). Five months following local hEPC transplantation, on the tissue and organ level, no inflammatory reaction or dysplastic change was evident at the transplanted site or in distant organs. Direct engraftment was evident as CD31 human antigens were detected lining vessel walls in the transplanted site. In distant organs human antigens were absent, negating biodistribution. Bone area fraction and bone height were doubled by hEPC transplantation without affecting mineral density and bone architecture. Additionally, local transplantation of hEPCs increased blood vessel density by nine-fold. Conclusions Local transplantation of hEPCs showed a positive safety profile. Furthermore, enhanced angiogenesis and osteogenesis without mineral density change was found. These results bring us one step closer to first-in-human trials using hEPCs for bone regeneration. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect