title: Adipose tissue-derived mesenchymal stem cells facilitate hematopoiesis in vitro and in vivo: advantages over bone marrow-derived mesenchymal stem cells.
abstract: Mesenchymal stem cells (MSCs) have emerged as a new therapeutic modality for reconstituting the hematopoietic microenvironment by improving engraftment in stem cell transplantation. However, the availability of conventional bone marrow (BM)-derived MSCs (BMSCs) is limited. Recent studies showed that a large number of MSCs can be easily isolated from fat tissue (adipose tissue-derived MSCs [ADSCs]). In this study, we extensively evaluated the hematopoiesis-supporting properties of ADSCs, which are largely unknown. In vitro coculture and progenitor assays showed that ADSCs generated significantly more granulocytes and progenitor cells from human hematopoietic stem cells (HSCs) than BMSCs. We found that ADSCs express the chemokine CXCL12, a critical regulator of hematopoiesis, at levels that are three fold higher than those with BMSCs. The addition of a CXCL12 receptor antagonist resulted in a lower yield of granulocytes from ADSC layers, whereas the addition of recombinant CXCL12 to BMSC cocultures promoted the growth of granulocytes. In vivo cell homing assays showed that ADSCs facilitated the homing of mouse HSCs to the BM better than BMSCs. ADSCs injected into the BM cavity of fatally irradiated mice reconstituted hematopoiesis more promptly than BMSCs and subsequently rescued mice that had received a low number of HSCs. Secondary transplantation experiments showed that ADSCs exerted favorable effects on long-term HSCs. These results suggest that ADSCs can be a promising therapeutic alternative to BMSCs.
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Nakao
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakayama
authors.forename: Takashi
authors.initials: T
authors.lastname: Yahata
authors.forename: Yukari
authors.initials: Y
authors.lastname: Muguruma
authors.forename: Shigeki
authors.initials: S
authors.lastname: Saito
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Miyata
authors.forename: Koji
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Tomoki
authors.initials: T
authors.lastname: Naoe
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D016026:Bone Marrow Transplantation; D002460:Cell Line; D054377:Chemokine CXCL12 / Q000378:metabolism; D006410:Hematopoiesis / Q000502:physiology*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D054377:Chemokine CXCL12