Cotransplantation with MSCs improves engraftment of HSCs after autologous intra-bone marrow transplantation in nonhuman primates

Masuda, Shigeo; Ageyama, Naohide; Shibata, Hiroaki; Obara, Yoko; Ikeda, Tamako; Takeuchi, Kengo; Ueda, Yasuji; Ozawa, Keiya; Hanazono, Yutaka

doi:10.1016/j.exphem.2009.07.008

Cited by 45 publications

(38 citation statements)

References 33 publications

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“…32 Likewise, co transplantation of BMderived stromal cells along with HSCs can be performed safely in humans and has been shown to improve engraftment in both humanized mouse and nonhuman primate models. [33][34][35] The extent and nature of the damage to BM stroma after exposure to IR remain elusive. In the present study, we provide evidence that BM stromal cell populations express markers of senescence in response to IR.…”

Section: Discussionmentioning

confidence: 99%

Ionizing radiation–induced expression of INK4a/ARF in murine bone marrow–derived stromal cell populations interferes with bone marrow homeostasis

Carbonneau

Despars

Rojas-Sutterlin

et al. 2012

Blood

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Alterations of the BM microenvironment have been shown to occur after chemoradiotherapy, during aging, and after genetic manipulations of telomere length. Nevertheless, whether BM stromal cells adopt senescent features in response to these events is unknown. In the present study, we provide evidence that exposure to ionizing radiation (IR) leads murine stromal BM cells to express senescence markers, namely senescence-associated ␤-galactosidase and increased p16 INK4a / p19 ARF expression. Long (8 weeks) after exposure of mice to IR, we observed a reduction in the number of stromal cells derived from BM aspirates, an effect that we found to be absent in irradiated Ink4a/ arf-knockout mice and to be mostly independent of the CFU potential of the stroma. Such a reduction in the number of BM stromal cells was specific, because stromal cells isolated from collagenasetreated bones were not reduced after IR. Surprisingly, we found that exposure to IR leads to a cellular nonautonomous and Ink4a/arf-dependent effect on lymphopoiesis. Overall, our results reveal the distinct sensitivity of BM stromal cell populations to IR and suggest that long-term residual damage to the BM microenvironment can influence hematopoiesis in an Ink4a/arf-dependent manner. (Blood. 2012; 119(3):717-726)

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Section: Discussionmentioning

confidence: 99%

Ionizing radiation–induced expression of INK4a/ARF in murine bone marrow–derived stromal cell populations interferes with bone marrow homeostasis

Carbonneau

Despars

Rojas-Sutterlin

et al. 2012

Blood

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“…During the initial phases of baboon fetal development, the urinary tract grows and develops comparably to humans accentuated by a late burst of growth during in late gestation [38]. A variety of studies in numerous fields comprising decades of research activity with NHPs as preclinical models have been used in the elucidation of physiological mechanisms [39][40][41]. As there is a paucity of information with regards to baboon bladder regeneration, our study is the first report on a NHP bladder augmentation model using an autologous source of BM MSCs.…”

Section: Discussionmentioning

confidence: 99%

A Nonhuman Primate Model for Urinary Bladder Regeneration Using Autologous Sources of Bone Marrow-Derived Mesenchymal Stem Cells

et al. 2011

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Animal models that have been used to examine the regenerative capacity of cell-seeded scaffolds in a urinary bladder augmentation model have ultimately translated poorly in the clinical setting. This may be due to a number of factors including cell types used for regeneration and anatomical/ physiological differences between lower primate species and their human counterparts. We postulated that mesenchymal stem cells (MSCs) could provide a cell source for partial bladder regeneration in a newly described nonhuman primate bladder (baboon) augmentation model. Cell-sorted2 baboon MSCs transduced with green fluorescent protein (GFP) were seeded onto small intestinal submucosa (SIS) scaffolds. Baboons underwent an approximate 40%-50% cystectomy followed by augmentation cystoplasty with the aforementioned scaffolds or controls and finally enveloped with omentum. Bladders from sham, unseeded SIS, and MSC/SIS scaffolds were subjected to trichrome, H&E, and immunofluorescent staining 10 weeks postaugmentation. Immunofluorescence staining for muscle markers combined with an anti-GFP antibody revealed that >90% of the cells were GFP Disclosure of potential conflicts of interest is found at the end of this article.

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“…38 In non-human primates, co-transplantation of MSCs improved HC engraftment after autologous intra-BM transplantation and this was associated with increased chimerism in the peripheral blood. 39 As already mentioned above, Kuci et al 13 showed that CD271 þ MSCs were capable of promoting significantly greater lymphoid engraftment, as compared to an unselected population of plastic-adherent MSCs, when co-transplanted with CD133 þ HCs in NOD/SCID mice.…”

Section: In Vivo Animal Models To Test the Engraftment-promoting Propmentioning

confidence: 95%

Mesenchymal stromal cells: a novel and effective strategy for facilitating engraftment and accelerating hematopoietic recovery after transplantation?

Bernardo

Cometa

Locatelli

2011

Bone Marrow Transplant

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Cotransplantation with MSCs improves engraftment of HSCs after autologous intra-bone marrow transplantation in nonhuman primates

Cited by 45 publications

References 33 publications

Ionizing radiation–induced expression of INK4a/ARF in murine bone marrow–derived stromal cell populations interferes with bone marrow homeostasis

Ionizing radiation–induced expression of INK4a/ARF in murine bone marrow–derived stromal cell populations interferes with bone marrow homeostasis

A Nonhuman Primate Model for Urinary Bladder Regeneration Using Autologous Sources of Bone Marrow-Derived Mesenchymal Stem Cells

Mesenchymal stromal cells: a novel and effective strategy for facilitating engraftment and accelerating hematopoietic recovery after transplantation?

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