Secretory profiles and wound healing effects of human amniotic fluid-derived mesenchymal stem cells.
Recent evidence shows that amniotic fluid (AF) contains multiple cell types derived from the developing fetus, and may represent a novel source of stem cells for cell therapy. In this study, we examined the paracrine factors released by human amniotic fluid-derived mesenchymal stem cells (AF-MSCs) and their ability to accelerate the wound-healing process by stimulating proliferation and migration of dermal fibroblasts. AF-MSCs expressed the typical MSC marker proteins CD13, CD29, and CD44 and differentiated into adipocytes, osteoblasts, and chondrocytes when exposed to the appropriate differentiation media. In addition, AF-MSC-conditioned media (AF-MSC-CM) significantly enhanced proliferation of dermal fibroblasts. Antibody-based protein array and enzyme-linked immunosorbent assay (ELISA) indicated that AF-MSC-CM contains various cytokines and chemokines that are known to be important in normal wound healing, including IL-8, IL-6, TGF-beta, TNFRI, VEGF, and EGF. Application of AF-MSC-CM significantly enhanced wound healing by dermal fibroblasts via the TGF-beta/SMAD2 pathway. Levels of p-SMAD2 were increased by AF-MSC-CM, and both the increase in p-SMAD2 and migration of dermal fibroblasts were blocked by inhibiting the TGF-beta/SMAD2 pathway. Moreover, in a mouse excisional wound model, AF-MSC-CM accelerated wound healing. These data provide the first evidence of the potential for AF-MSC-CM in the treatment of skin wounds.
Yoon
Byung Sun
BS
Laboratory of Cell Function Regulation, College of Life Sciences and Biotechnology, Korea University, Anam-dong, Seongbuk-gu, Seoul, Republic of Korea.
Moon
Jai-Hee
JH
Jun
Eun Kyoung
EK
Kim
Jonggun
J
Maeng
Isaac
I
Kim
Jun Sung
JS
Lee
Jung Han
JH
Baik
Cheong Soon
CS
Kim
Aeree
A
Cho
Kyoung Shik
KS
Lee
Jang Ho
JH
Lee
Hwang Heui
HH
Whang
Kwang Youn
KY
You
Seungkwon
S
D000653:Amniotic Fluid / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D002999:Clone Cells; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D020405:Dermis / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D040081:Protein Array Analysis; D051899:Smad2 Protein / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
D017077:Culture Media, Conditioned; D016207:Cytokines; D051899:Smad2 Protein