Efficacy and safety of human adipose tissue-derived mesenchymal stem cells for supporting hematopoiesis.
We have demonstrated that adipose tissue-derived mesenchymal stem cells (ADSCs) from mice are capable of reconstituting the hematopoietic microenvironment, and facilitate hematopoiesis more effectively than bone marrow-derived mesenchymal stem cells (BMSCs) in mouse. The ready accessibility of fat tissue rich in MSCs and the higher hematopoiesis-supporting capacities of ADSCs suggest that ADSCs might represent a new therapeutic modality for the regeneration of impaired hematopoiesis. As a further step towards their use in clinical practice, we established human BMSCs and ADSCs from healthy volunteers of similar age, and compared their proliferation capacities, hematopoiesis-supporting properties, and safety. In vitro cell proliferation studies revealed that ADSCs have a higher population doubling number than BMSCs. In vitro co-culture assays showed that ADSCs not only support human CD34(+) peripheral blood stem cells (PBSCs), but also yield significantly more non-adherent hematic cells than BMSCs. In vitro progenitor assays revealed that ADSCs promote a higher frequency of early progenitors than do BMSCs. Interestingly, BM cellularity in irradiated mice that had received ADSCs tended to be higher than that of mice treated with BMSCs. When MSCs were injected into the BM cavity of tibiae, we observed no evidence of MSC-induced toxicity either during or after treatment. In addition, no microscopic abnormalities were observed in the bone marrow and major organs.
Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Satoshi
S
Nishiwaki
Takayuki
T
Nakayama
Shigeki
S
Saito
Hiroki
H
Mizuno
Takenori
T
Ozaki
Yoshiyuki
Y
Takahashi
Shoichi
S
Maruyama
Tetsuya
T
Nishida
Makoto
M
Murata
Seiji
S
Kojima
Tomoki
T
Naoe
D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000166:cytology; D008099:Liver / Q000166:cytology; D008168:Lung / Q000166:cytology; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009206:Myocardium / Q000166:cytology; D013154:Spleen; D055815:Young Adult
D018952:Antigens, CD34