Generation of an Immortalized Human Adipose-Derived Mesenchymal Stromal Cell Line Suitable for Wound Healing Therapy

Adipose-derived mesenchymal stromal cells (ADSC) are a promising source for cellular therapy of chronic wounds. However, the limited life span during in vitro expansion impedes their extensive use in clinical applications and basic research. We hypothesize that by introduction of an ectopic expressi...

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Bibliographic Details
Published in:International journal of molecular sciences 2022-08, Vol.23 (16), p.8925
Main Authors: Iacomi, Daniela-Madalina, Rosca, Ana-Maria, Tutuianu, Raluca, Neagu, Tiberiu Paul, Pruna, Vasile, Simionescu, Maya, Titorencu, Irina
Format: Article
Language:English
Subjects:
Adipocytes
adipose-derived stromal cells
Body fat
Cell proliferation
Cloning
Codification
Diabetes
Ectopic expression
Endothelial cells
Fibroblasts
Flow cytometry
Growth factors
hTERT
immortalization
Keratinocytes
lentiviral transduction
Mesenchyme
Population
Secretome
Senescence
Skin
Stromal cells
Telomerase
Telomerase reverse transcriptase
Wound healing
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Summary:Adipose-derived mesenchymal stromal cells (ADSC) are a promising source for cellular therapy of chronic wounds. However, the limited life span during in vitro expansion impedes their extensive use in clinical applications and basic research. We hypothesize that by introduction of an ectopic expression of telomerase into ADSC, the cells’ lifespans could be significantly extended. To test this hypothesis, we aimed at engineering an immortalized human ADSC line using a lentiviral transduction with human telomerase (hTERT). ADSC were transduced with a third-generation lentiviral system and a hTERT codifying plasmid (pLV-hTERT-IRES-hygro). A population characterized by increased hTERT expression, extensive proliferative potential and remarkable (potent) multilineage differentiation capacity was selected. The properties for wound healing of this immortalized ADSC line were assessed after 17 passages. Their secretome induced the proliferation and migration of keratinocytes, dermal fibroblasts, and endothelial cells similarly to untransduced ADSC. Moreover, they sustained the complete re-epithelialization of a full thickness wound performed on a skin organotypic model. In summary, the engineered immortalized ADSC maintain the beneficial properties of parent cells and could represent a valuable and suitable tool for wound healing in particular, and for skin regenerative therapy in general.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23168925