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Administration of Cripto in <scp>GRP</scp> 78 overexpressed human <scp>MSC</scp> s enhances stem cell viability and angiogenesis during human <scp>MSC</scp> transplantation therapy
- Source :
- Cell Proliferation. 51
- Publication Year :
- 2018
- Publisher :
- Wiley, 2018.
-
Abstract
- OBJECTIVES: The purpose of this study was to explore the effectiveness of concurrent GRP78 overexpression combined with Cripto on hMSC proliferation and migration both in vitro and in vivo. Specifically, we explored whether the treatment enhances effectiveness of hMSC transplantation in ischaemic tissue. MATERIALS AND METHODS: Human MSCs obtained from human adipose tissue were cultured in α‐minimum essential medium (Hyclone, Logan, UT, USA) supplemented with 10% (v/v) foetal bovine serum (Hyclone), 100 U mL(−1) penicillin and 100 μg mL(−1) streptomycin. Murine hindlimb ischaemic model was generated with 8‐week‐old male nude BALB/c mice (Biogenomics, Seoul, Korea) maintained under a 12‐h light/dark cycle following the established protocol with minor modification. Cellular injection was performed no later than 3 hour after surgery. Lipofectamine transfection, single‐cell cultivation assay, transwell assay, scratch wound‐healing migration assay, immunohistochemistry and western blotting assays were performed. RESULTS: Overexpression of GRP78 along with Cripto enhanced hMSC proliferation, migration and invasion. It increased interaction of surface GRP78 receptor with Cripto via JAK2/STAT3 pathway. We confirmed our proposed mechanism by showing that treatment with GRP78 antibody blocks the enhancement in vitro. In vivo, we observed that Cripto induced by the hypoxic environment in hindlimb ischaemic model interacts with the overexpressed GRP78 and increases hMSC proliferation, migration and invasion potentials as well as angiogenesis around transplanted ischaemic site via cytokine secretions. CONCLUSIONS: These results demonstrate supporting evidences that GRP78‐Cripto combination technique offers novel strategy to enhance MSC proliferation, migration and invasion potentials as well as angiogenesis around ischaemic site, ultimately facilitating MSC‐based transplantation therapy in ischaemic conditions.
- Subjects :
- Male
STAT3 Transcription Factor
0301 basic medicine
Cell Survival
Angiogenesis
Mice, Nude
Biology
GPI-Linked Proteins
Mesenchymal Stem Cell Transplantation
Cripto
Cell Line
Mice
03 medical and health sciences
Cell Movement
Ischemia
In vivo
Animals
Humans
Endoplasmic Reticulum Chaperone BiP
Heat-Shock Proteins
Cell Proliferation
Mice, Inbred BALB C
Wound Healing
Migration Assay
Neovascularization, Pathologic
Stem Cells
Mesenchymal stem cell
Mesenchymal Stem Cells
Original Articles
Cell Biology
General Medicine
Janus Kinase 2
Cell Hypoxia
Neoplasm Proteins
Transplantation
030104 developmental biology
Lipofectamine
Cancer research
Intercellular Signaling Peptides and Proteins
Stem cell
Signal Transduction
Subjects
Details
- ISSN :
- 13652184 and 09607722
- Volume :
- 51
- Database :
- OpenAIRE
- Journal :
- Cell Proliferation
- Accession number :
- edsair.doi.dedup.....1be04192d0e245896db18ae1904bd17d