title: Cotransplantation with MSCs improves engraftment of HSCs after autologous intra-bone marrow transplantation in nonhuman primates.
abstract: OBJECTIVE
  Hematopoietic stem cells (HSCs) reside in the osteoblastic niche, which consists of osteoblasts. Mesenchymal stromal cells (MSCs) have an ability to differentiate into osteoblasts. Here, using nonhuman primates, we investigated the effects of cotransplantation with MSCs on the engraftment of HSCs after autologous intra-bone marrow transplantation.
  
  
  METHODS
  From three cynomolgus monkeys, CD34-positive cells (as HSCs) and MSCs were obtained. The former were divided into two equal aliquots and each aliquot was genetically marked with a distinctive retroviral vector to track the in vivo fate. Each HSC aliquot with or without MSCs was autologously injected into the bone marrow (BM) cavity of right or left side, enabling the comparison of in vivo fates of the two HSC grafts in the same body.
  
  
  RESULTS
  In the three monkeys, CD34(+) cells transplanted with MSCs engrafted 4.4, 6.0, and 1.6 times more efficiently than CD34(+) cells alone, as assessed by BM colony polymerase chain reaction. In addition, virtually all marked cells detected in the peripheral blood were derived from the cotransplantation aliquots. Notably, colony-forming units derived from the cotransplantation aliquots were frequently detected in BM distant sites from the injection site, implying that cotransplantation with MSCs also restored the ability of gene-marked HSCs to migrate and achieve homing in the distant BM.
  
  
  CONCLUSIONS
  Cotransplantation with MSCs would improve the efficacy of transplantation of gene-modified HSCs in primates, with enhanced engraftment in BM as well as increased chimerism in peripheral blood through migration and homing.
authors.affiliation: Division of Regenerative Medicine, Center for Molecular Medicine, Jichi Medical University, Tochigi 329-0498, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Masuda
authors.forename: Naohide
authors.initials: N
authors.lastname: Ageyama
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shibata
authors.forename: Yoko
authors.initials: Y
authors.lastname: Obara
authors.forename: Tamako
authors.initials: T
authors.lastname: Ikeda
authors.forename: Kengo
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Ueda
authors.forename: Keiya
authors.initials: K
authors.lastname: Ozawa
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hanazono
mesh_terms: D000818:Animals; D019070:Cell Lineage; D002478:Cells, Cultured / Q000637:transplantation; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000032:analysis; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D008252:Macaca fascicularis; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D010006:Osteoblasts / Q000166:cytology; D017154:Stromal Cells / Q000637:transplantation; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous