Studies of the route of administration and role of conditioning with radiation on unrelated allogeneic mismatched mesenchymal stem cell engraftment in a nonhuman primate model

Mahmud, Nadim; Pang, Wenxin; Cobbs, Carrington; Alur, Prasad; Borneman, Jade; Dodds, Robert A.; Archambault, Michael; Devine, Steven M.; Turian, J; Bartholomew, Amelia; Vanguri, Padmavathy; Mackay, Alastair M.; Young, Randell G.; Hoffman, Ronald

doi:10.1016/j.exphem.2004.02.010

Cited by 54 publications

(36 citation statements)

References 37 publications

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“…Details of the PCR findings are found in Table 2. The findings are consistent with results from animal models, where MSCs have been found to be trapped in the lung within minutes of intravenous infusion and cleared from the circulation [6,8,17]. Of the four patients positive for MSC donor DNA in the lungs, evidence of microembolisms could be found on histological examination in one patient, 1071, described below.…”

Section: Resultssupporting

confidence: 78%

Analysis of Tissues Following Mesenchymal Stromal Cell Therapy in Humans Indicates Limited Long-Term Engraftment and No Ectopic Tissue Formation

et al. 2012

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Mesenchymal stromal cells (MSCs) are explored as a novel treatment for a variety of medical conditions. Their fate after infusion is unclear, and long-term safety regarding malignant transformation and ectopic tissue formation has not been addressed in patients. We examined autopsy material from 18 patients who had received human leukocyte antigen (HLA)-mismatched MSCs, and 108 tissue samples from 15 patients were examined by PCR. No signs of ectopic tissue formation or malignant tumors of MSC-donor origin were found on macroscopic or histological examination. MSC donor DNA was detected in one or several tissues including lungs, lymph nodes, and intestine in eight patients at levels from 1/100 to <1/1,000. Detection of MSC donor DNA was negatively correlated with time from infusion to sample collection, as DNA was detected from nine of 13 MSC infusions given within 50 days before sampling but from only two of eight infusions given earlier. There was no correlation between MSC engraftment and treatment response. We conclude that MSCs appear to mediate their function through a “hit and run” mechanism. The lack of sustained engraftment limits the long-term risks of MSC therapy.

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Section: Resultssupporting

confidence: 78%

Analysis of Tissues Following Mesenchymal Stromal Cell Therapy in Humans Indicates Limited Long-Term Engraftment and No Ectopic Tissue Formation

et al. 2012

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“…In a preclinical study, the effect of the route of mesenchymal stem cell (MSC) administration was tested in primates. 13 The investigators did not find intrabone MSC administration to be more effective than i.v. MSC delivery.…”

Section: Discussionmentioning

confidence: 99%

“…[4][5][6][7][8][9][10][11][12] Recently this promising new strategy of intraosseous stem cell engraftment was applied in nonhuman primates under conditioning with radiation. 13 We previously reported the effect of different routes and dosages of BMC transplantation on chimerism induction in the peripheral blood.…”

Section: Introductionmentioning

confidence: 99%

Donor–origin cell engraftment after intraosseous or intravenous bone marrow transplantation in a rat model

Klimczak

Ünal

Jankowska

et al. 2007

Bone Marrow Transplant

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We compared the effects of intraosseous BMT with those of standard i.v. BMT on the efficacy on donor-cell engraftment into the BM and lymphoid organs across an MHC barrier in rats. Twenty-four intraosseous and 24 i.v. BMTs were performed from 48 ACI (RT1 a ) donors to 48 Lewis (RT1 l ) recipients. Each transplant group received either intraosseous or i.v. BMT. Groups I and II served as controls without immunosuppression (n ¼ 16); groups III and IV received cyclosporine monotherapy (n ¼ 16); and V and VI received ab-TCR monoclonal antibody and cyclosporine A (ab-TCR/CsA) for 7 days (n ¼ 16). In each group, four rats received 35 Â 10 6 transplanted bone marrow cells (BMCs) and four received 70 Â 10 6 cells. All animals survived without GVHD. Mean (7s.d.) donorcell engraftment into BM of recipients after intraosseous BMT was 7.9% (71.3%) in recipients receiving ab-TCR-CsA and 70 Â 10 6 BMCs, and 4.2% (71.4%) in recipients after i.v. transplantation. The seeding efficacy of donor cells into lymphoid tissue was greater after intraosseous BMT and ab-TCR-CsA than after standard i.v. transplantation. In our model, intraosseous BMT facilitated donor-cell engraftment under short-term immunodepletive ab-TCR/CsA protocol, which resulted in a temporary state of immune unresponsiveness.

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“…50,51 In a NOD/SCID xenograft model, Yahata et al 50,51 showed that CXCR4 also plays a role in human HSC transplantation by the intra-BM route. However Mahmud et al 53 found that the intra-BM route was not more effective than the intravenous route in delivering MSC grafts. The intra-BM strategy seems to hold promise for future clinical application and deserves further investigation.…”

Section: Discussionmentioning

confidence: 99%

Regulation of CXCR4 expression in human mesenchymal stem cells by cytokine treatment: role in homing efficiency in NOD/SCID mice

Shi¹,

Li²,

Liao³

et al. 2007

Haematologica

300

225

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Studies of the route of administration and role of conditioning with radiation on unrelated allogeneic mismatched mesenchymal stem cell engraftment in a nonhuman primate model

Cited by 54 publications

References 37 publications

Analysis of Tissues Following Mesenchymal Stromal Cell Therapy in Humans Indicates Limited Long-Term Engraftment and No Ectopic Tissue Formation

Analysis of Tissues Following Mesenchymal Stromal Cell Therapy in Humans Indicates Limited Long-Term Engraftment and No Ectopic Tissue Formation

Donor–origin cell engraftment after intraosseous or intravenous bone marrow transplantation in a rat model

Regulation of CXCR4 expression in human mesenchymal stem cells by cytokine treatment: role in homing efficiency in NOD/SCID mice

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