Direct lineage tracing reveals Activin-a potential for improved pancreatic homing of bone marrow mesenchymal stem cells and efficient ß-cell regeneration in vivo
BACKGROUND: Despite the potential, bone marrow-derived mesenchymal stem cells (BMSCs) show limitations for beta (ß)-cell replacement therapy due to inefficient methods to deliver BMSCs into pancreatic lineage. In this study, we report TGF-ß family member protein, Activin-a potential to stimulate efficient pancreatic migration, enhanced homing and accelerated ß-cell differentiation.
METHODS: Lineage tracing of permanent green fluorescent protein (GFP)- tagged donor murine BMSCs transplanted either alone or in combination with Activin-a in diabetic mice displayed potential ß-cell regeneration and reversed diabetes.
RESULTS: Pancreatic histology of Activin-a treated recipient mice reflected high GFP+BMSC infiltration into damaged pancreas with normalized fasting blood glucose and elevated serum insulin. Whole pancreas FACS profiling of GFP+ cells displayed significant homing of GFP+BMSC with Activin-a treatment (6%) compared to BMSCs alone transplanted controls (0.5%). Within islets, approximately 5% GFP+ cells attain ß-cell signature (GFP+ Ins+) with Activin-a treatment versus controls. Further, double immunostaining for mesenchymal stem cell markers CD44+/GFP+ in infiltrated GFP+BMSC deciphers substantial endocrine reprogramming and ß-cell differentiation (6.4% Ins+/GFP+) within 15 days.
CONCLUSION: Our investigation thus presents a novel pharmacological approach for stimulating direct migration and homing of therapeutic BMSCs that re-validates BMSC potential for autologous stem cell transplantation therapy in diabetes.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Stem cell research & therapy - 11(2020), 1 vom: 30. Juli, Seite 327 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dadheech, Nidheesh [VerfasserIn] |
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| Links: |
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| Themen: |
ß-cell differentiation |
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| Anmerkungen: |
Date Completed 18.06.2021 Date Revised 18.06.2021 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1186/s13287-020-01843-z |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM313074364 |
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| 100 | 1 | |a Dadheech, Nidheesh |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Direct lineage tracing reveals Activin-a potential for improved pancreatic homing of bone marrow mesenchymal stem cells and efficient ß-cell regeneration in vivo |
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| 500 | |a Date Completed 18.06.2021 | ||
| 500 | |a Date Revised 18.06.2021 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Despite the potential, bone marrow-derived mesenchymal stem cells (BMSCs) show limitations for beta (ß)-cell replacement therapy due to inefficient methods to deliver BMSCs into pancreatic lineage. In this study, we report TGF-ß family member protein, Activin-a potential to stimulate efficient pancreatic migration, enhanced homing and accelerated ß-cell differentiation | ||
| 520 | |a METHODS: Lineage tracing of permanent green fluorescent protein (GFP)- tagged donor murine BMSCs transplanted either alone or in combination with Activin-a in diabetic mice displayed potential ß-cell regeneration and reversed diabetes | ||
| 520 | |a RESULTS: Pancreatic histology of Activin-a treated recipient mice reflected high GFP+BMSC infiltration into damaged pancreas with normalized fasting blood glucose and elevated serum insulin. Whole pancreas FACS profiling of GFP+ cells displayed significant homing of GFP+BMSC with Activin-a treatment (6%) compared to BMSCs alone transplanted controls (0.5%). Within islets, approximately 5% GFP+ cells attain ß-cell signature (GFP+ Ins+) with Activin-a treatment versus controls. Further, double immunostaining for mesenchymal stem cell markers CD44+/GFP+ in infiltrated GFP+BMSC deciphers substantial endocrine reprogramming and ß-cell differentiation (6.4% Ins+/GFP+) within 15 days | ||
| 520 | |a CONCLUSION: Our investigation thus presents a novel pharmacological approach for stimulating direct migration and homing of therapeutic BMSCs that re-validates BMSC potential for autologous stem cell transplantation therapy in diabetes | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Activin-a | |
| 650 | 4 | |a Bone marrow mesenchymal stem cells | |
| 650 | 4 | |a Lineage tracing | |
| 650 | 4 | |a ß-cell differentiation | |
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| 700 | 1 | |a Srivastava, Abhay |e verfasserin |4 aut | |
| 700 | 1 | |a Vakani, Mitul |e verfasserin |4 aut | |
| 700 | 1 | |a Shrimali, Paresh |e verfasserin |4 aut | |
| 700 | 1 | |a Bhonde, Ramesh |e verfasserin |4 aut | |
| 700 | 1 | |a Gupta, Sarita |e verfasserin |4 aut | |
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