Allogeneic human umbilical cord Wharton’s jelly stem cells increase several-fold the expansion of human cord blood CD34+ cells both in vitro and in vivo
| Autor: | Chui-Yee Fong, Hao Daniel Lin, Arijit Biswas, Ariff Bongso |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Stromal cell CD34 Ex vivo expansion Medicine (miscellaneous) Antigens CD34 Biochemistry Genetics and Molecular Biology (miscellaneous) Umbilical Cord Mouse model lcsh:Biochemistry 03 medical and health sciences Mice 0302 clinical medicine Wharton's jelly medicine Animals Humans CD90 Oxidative phosphorylation lcsh:QD415-436 Wharton Jelly Conditioned medium Cells Cultured lcsh:R5-920 Umbilical cord blood CD34+ cells Chemistry Research Mesenchymal stem cell Hematopoietic Stem Cell Transplantation Mesenchymal Stem Cells NADH Dehydrogenase Cell Biology Fetal Blood Molecular biology Human Wharton’s jelly stem cells Mitochondria 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cord blood Molecular Medicine Bone marrow Stem cell lcsh:Medicine (General) Glycolysis |
| Zdroj: | Stem Cell Research & Therapy, Vol 11, Iss 1, Pp 1-18 (2020) Stem Cell Research & Therapy |
| ISSN: | 1757-6512 |
| Popis: | Background The transplantation of human umbilical cord blood (UCB) CD34+ cells has been successfully used to treat hematological disorders but one major limitation has been the low cell numbers available. Mesenchymal stem cells (MSCs) lying within the bone marrow in vivo behave like a scaffold on which CD34+ cells interact and proliferate. We therefore evaluated the use of allogeneic MSCs from the human UC Wharton’s jelly (hWJSCs) as stromal support for the ex vivo expansion of CD34+ cells. Methods We performed an in-depth evaluation of the primitiveness, migration, adhesion, maturation, mitochondrial behavior, and pathway mechanisms of this platform using conventional assays followed by the evaluation of engraftment potential of the expanded CD34+ cells in an in vivo murine model. Results We demonstrate that hWJSCs and its conditioned medium (hWJSC-CM) support the production of significantly high fold changes of CD34+, CD34+CD133+, CD34+CD90+, CD34+ALDH+, CD34+CD45+, and CD34+CD49f+ cells after 7 days of interaction when compared to controls. In the presence of hWJSCs or hWJSC-CM, the CD34+ cells produced significantly more primitive CFU-GEMM colonies, HoxB4, and HoxA9 gene expression and lower percentages of CD34+CXCR4+ cells. There were also significantly higher N-cadherin+ cell numbers and increased cell migration in transwell migration assays. The CD34+ cells expanded with hWJSCs had significantly lower mitochondrial mass, mitochondrial membrane potential, and oxidative stress. Green Mitotracker-tagged mitochondria from CD34+ cells were observed lying within red CellTracker-tagged hWJSCs under confocal microscopy indicating mitochondrial transfer via tunneling nanotubes. CD34+ cells expanded with hWJSCs and hWJSC-CM showed significantly reduced oxidative phosphorylation (ATP6VIH and NDUFA10) and increased glycolytic (HIF-1a and HK-1) pathway-related gene expression. CD34+ cells expanded with hWJSCs for 7 days showed significant greater CD45+ cell chimerism in the bone marrow of primary and secondary irradiated mice when transplanted intravenously. Conclusions In this report, we confirmed that allogeneic hWJSCs provide an attractive platform for the ex vivo expansion of high fold numbers of UCB CD34+ cells while keeping them primitive. Allogeneic hWJSCs are readily available in abundance from discarded UCs, can be easily frozen in cord blood banks, thawed, and then used as a platform for UCB-HSC expansion if numbers are inadequate. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|