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Restoring mammary gland structures and functions with autogenous cell therapy
- Source :
- Biomaterials. 277:121075
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- In somatic cell reprogramming, cells must escape the somatic cell-specific gene expression program to adopt other cell fates. Here, in vitro chemical induction with RepSox generated chemically induced mammary epithelial cells (CiMECs) with milk secreting functions from goat ear fibroblasts (GEFs). Transplanted CiMECs regenerated the normal mammary gland structure with milk-secreting functions in nude mice. Single-cell RNA sequencing revealed that during the reprogramming process, GEFs may sequentially undergo embryonic ectoderm (EE)-like and different MEC developmental states and finally achieve milk secreting functions, bypassing the pluripotent state. Mechanistically, Smad3 upregulation induced by transforming growth factor β (TGFβ) receptor 1 (TGFβR1) downregulation led to GEF reprogramming into CiMECs without other reprogramming factors. The TGFβR1-Smad3 regulatory effects will provide new insight into the TGFβ signaling pathway regulation of somatic cell reprogramming. These findings suggest an innovative strategy for autogenous cell therapy for mammary gland defects and the production of transgenic mammary gland bioreactors.
- Subjects :
- Somatic cell
Goats
Cell
Mammary gland
Cell- and Tissue-Based Therapy
Biophysics
Mice, Nude
Epithelial Cells
Bioengineering
Biology
Cell biology
Biomaterials
Cell therapy
Mice
Mammary Glands, Animal
medicine.anatomical_structure
Downregulation and upregulation
Mechanics of Materials
Ceramics and Composites
medicine
Animals
Signal transduction
Reprogramming
Transforming growth factor
Subjects
Details
- ISSN :
- 01429612
- Volume :
- 277
- Database :
- OpenAIRE
- Journal :
- Biomaterials
- Accession number :
- edsair.doi.dedup.....2c4419e63ac13f1286877a08f6d087e6