Abstract
Bone marrow-derived human mesenchymal stem cells (hMSCs) possess multipotent differentiation capabilities and are a potent source of paracrine factors. We show how the epidermal keratinocyte can direct hMSC differentiation selectively. Keratinocytes and hMSCs were either cocultured in physical contact (contact cocultures), or separated without physical contact using a transwell insert (noncontact cocultures). We also delivered hMSCs into an ex vivo human excisional wound where subpopulations of the hMSCs were either in contact or were physically separated from the epidermal keratinocytes. In comparison to control hMSCs that were not cocultured, contact cocultured hMSCs adopted an epithelial morphology and expressed keratinocyte markers while noncontact coculutred hMSCs, surprisingly, adopted phenotypes that resembled myofibroblast and early neural lineage, both of which are of dermal origin. Cell fusion was not a requirement in in vitro contact cocultures, as determined by fluorescence-activated cell sorting (FACS) and fluorescence in situ hybridization analysis (FISH). To the best of our knowledge, this work provides the first example of hMSC differentiation into different lineages depending on their proximity to a single cell type.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 122-131 |
| Number of pages | 10 |
| Journal | FASEB Journal |
| Volume | 25 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2011 |
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Keywords
- Coculture
- Ex vivo
- Healing
- Skin
- Wound
ASJC Scopus subject areas
- Biochemistry
- Biotechnology
- Genetics
- Molecular Biology
Cite this
Keratinocyte proximity and contact can play a significant role in determining mesenchymal stem cell fate in human tissue. / Sivamani, Raja K; Schwartz, Michael P.; Anseth, Kristi S.; Isseroff, Roslyn Rivkah.
In: FASEB Journal, Vol. 25, No. 1, 01.2011, p. 122-131.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Keratinocyte proximity and contact can play a significant role in determining mesenchymal stem cell fate in human tissue
AU - Sivamani, Raja K
AU - Schwartz, Michael P.
AU - Anseth, Kristi S.
AU - Isseroff, Roslyn Rivkah
PY - 2011/1
Y1 - 2011/1
N2 - Bone marrow-derived human mesenchymal stem cells (hMSCs) possess multipotent differentiation capabilities and are a potent source of paracrine factors. We show how the epidermal keratinocyte can direct hMSC differentiation selectively. Keratinocytes and hMSCs were either cocultured in physical contact (contact cocultures), or separated without physical contact using a transwell insert (noncontact cocultures). We also delivered hMSCs into an ex vivo human excisional wound where subpopulations of the hMSCs were either in contact or were physically separated from the epidermal keratinocytes. In comparison to control hMSCs that were not cocultured, contact cocultured hMSCs adopted an epithelial morphology and expressed keratinocyte markers while noncontact coculutred hMSCs, surprisingly, adopted phenotypes that resembled myofibroblast and early neural lineage, both of which are of dermal origin. Cell fusion was not a requirement in in vitro contact cocultures, as determined by fluorescence-activated cell sorting (FACS) and fluorescence in situ hybridization analysis (FISH). To the best of our knowledge, this work provides the first example of hMSC differentiation into different lineages depending on their proximity to a single cell type.
AB - Bone marrow-derived human mesenchymal stem cells (hMSCs) possess multipotent differentiation capabilities and are a potent source of paracrine factors. We show how the epidermal keratinocyte can direct hMSC differentiation selectively. Keratinocytes and hMSCs were either cocultured in physical contact (contact cocultures), or separated without physical contact using a transwell insert (noncontact cocultures). We also delivered hMSCs into an ex vivo human excisional wound where subpopulations of the hMSCs were either in contact or were physically separated from the epidermal keratinocytes. In comparison to control hMSCs that were not cocultured, contact cocultured hMSCs adopted an epithelial morphology and expressed keratinocyte markers while noncontact coculutred hMSCs, surprisingly, adopted phenotypes that resembled myofibroblast and early neural lineage, both of which are of dermal origin. Cell fusion was not a requirement in in vitro contact cocultures, as determined by fluorescence-activated cell sorting (FACS) and fluorescence in situ hybridization analysis (FISH). To the best of our knowledge, this work provides the first example of hMSC differentiation into different lineages depending on their proximity to a single cell type.
KW - Coculture
KW - Ex vivo
KW - Healing
KW - Skin
KW - Wound
UR - http://www.scopus.com/inward/record.url?scp=79251536178&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79251536178&partnerID=8YFLogxK
U2 - 10.1096/fj.09-148775
DO - 10.1096/fj.09-148775
M3 - Article
C2 - 20847231
AN - SCOPUS:79251536178
VL - 25
SP - 122
EP - 131
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 1
ER -