Microvesicles derived from Alde-Low EPCs support the wound healing capacity of AT-MSCs.
Mesenchymal stem cells (MSCs) are defined as multipotent cells that can give rise to various kinds of differentiated mesenchymal cells, and are thus considered to be useful for clinical therapy. However, the big hurdles of MSC therapy are the inability of MSCs to reach the appropriate tissues or sites with high efficiency and engraftment after transplantation. In this study, we investigated how adipose tissue-derived MSCs (AT-MSCs) improve their homing ability after intravenous injection. We previously found that human endothelial progenitor cells with low aldehyde dehydrogenase activity (Alde-Low EPCs) are suitable for the treatment of ischemic tissues. In addition, we demonstrated that microvesicles (MVs) derived from Alde-Low EPCs possessed the ability to improve the homing ability of non-functional Alde-High EPCs, resulting in wound healing. We initially transfected MVs derived from Alde-Low EPCs (EMVs) to human AT-MSCs, which were originally unable to cure ischemic tissues by intravenous transplantation. Remarkably, AT-MSC transfected EMVs dramatically repaired the ischemic skin flap compared with AT-MSC derived-MV (MMVs) transfected AT-MSCs or control AT-MSCs. We then found that the expression of CXCR4, an important chemokine receptor for cell migration, was highly elevated in EMV-transfected AT-MSCs. Moreover, AT-MSCs transfected with EMVs, but not control AT-MSCs, migrated to wound sites after intravenous injection. Consequently, CD45(+) inflammatory cells were successfully recruited at the wound sites after the injection of EMV-transfected AT-MSCs. These results demonstrate that EMVs are a useful source to improve the homing ability and wound healing ability of MSCs at the wound sites.
Graduate School of Comprehensive Human Sciences, Laboratory of Regenerative Medicine and Stem Cell Biology, University of Tsukuba, 1-1-1 Tsukuba, 305-8575 Japan.
Tran Cam
TC
Tu
Graduate School of Comprehensive Human Sciences, Laboratory of Regenerative Medicine and Stem Cell Biology, University of Tsukuba, 1-1-1 Tsukuba, 305-8575 Japan.
Toshiharu
T
Yamashita
Graduate School of Comprehensive Human Sciences, Laboratory of Regenerative Medicine and Stem Cell Biology, University of Tsukuba, 1-1-1 Tsukuba, 305-8575 Japan; Ph.D. Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba, 1-1-1 Tsukuba, 305-8575 Japan.
Toshiki
T
Kato
Graduate School of Comprehensive Human Sciences, Laboratory of Regenerative Medicine and Stem Cell Biology, University of Tsukuba, 1-1-1 Tsukuba, 305-8575 Japan.
Masumi
M
Nagano
Graduate School of Comprehensive Human Sciences, Laboratory of Regenerative Medicine and Stem Cell Biology, University of Tsukuba, 1-1-1 Tsukuba, 305-8575 Japan.
Nhu Thuy
NT
Trinh
Department of Obstetrics and Gynecology, University of Tsukuba, 1-1-1 Tsukuba, 305-8575 Japan.
Hiromi
H
Hamada
Department of Cardiovascular Surgery, University of Tsukuba, 1-1-1 Tsukuba, 305-8575 Japan.
Fujio
F
Sato
Laboratory of Molecular Pathophysiology, Faculty of Pharmacy, Takasaki University of Health and Welfare, Takasaki, 370-0033 Japan.
Kinuko
K
Ohneda
Graduate School of Comprehensive Human Sciences, Laboratory of Regenerative Medicine and Stem Cell Biology, University of Tsukuba, 1-1-1 Tsukuba, 305-8575 Japan.
Mami
M
Matsuo-Takasaki
Graduate School of Comprehensive Human Sciences, Laboratory of Regenerative Medicine and Stem Cell Biology, University of Tsukuba, 1-1-1 Tsukuba, 305-8575 Japan. Electronic address: oohneda@md.tsukuba.ac.jp.
Osamu
O
Ohneda
D000818:Animals; D066026:Endothelial Progenitor Cells / Q000166:cytology*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014945:Wound Healing
Endothelial progenitor cells; Mesenchymal stem cells; Microvesicles; Migration; Wound healing