Mesenchymal stem cells distribute to a wide range of tissues following systemic infusion into nonhuman primates

Devine, Steven M.; Cobbs, Carrington; Jennings, M. Kent; Bartholomew, Amelia; Hoffman, Ronald

doi:10.1182/blood-2002-06-1830

Cited by 665 publications

(456 citation statements)

References 17 publications

(29 reference statements)

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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%

“…When injected into fetal sheep, individual MSCs show site-specific differentiation [5]. In non-human adult primates, engraftment is lower, but both autologous and allogeneic MSCs can be detected in a wide range of organs [5][6][7]. However, a large proportion of MSCs are trapped either in the lung during first passage after intravenous infusion or in the microvasculature when infused on the arterial side [8,9].…”

Section: Introductionmentioning

confidence: 99%

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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%

Section: Introductionmentioning

confidence: 99%

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 general, allogeneic MSC, when infused in MHCmismatched recipients (even with no immunosuppression), home to a wide range of tissues and persist in the host [36,70]. Notably, the i.v.…”

Section: Msc-mediated Immunological Effects In Vivomentioning

confidence: 99%

Immunoregulatory function of mesenchymal stem cells

2006

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Mesenchymal stem cells (MSC) are a rare subset of stem cells residing in the bone marrow where they closely interact with hematopoietic stem cells and support their growth and differentiation. MSC can differentiate into multiple mesenchymal and non‐mesenchymal lineages, providing a promising tool for tissue repair. In addition, MSC suppress many T cell, B cell and NK cell functions and may affect also dendritic cell activities. Due to their limited immunogenicity, MSC are poorly recognized by HLA‐incompatible hosts. Based on these unique properties, MSC are currently under investigation for their possible use to treat immuno‐mediated diseases. However, both their condition of immunoprivilege and their immunosuppressive function have recently been challenged when analyzed under particular experimental conditions. Thus, it is likely that MSC effects on the immune system may be deeply influenced not only by cell‐to‐cell interactions, but also by environmental factors shaping their phenotype and functions.

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“…In vitro, they inhibit the proliferation of T lymphocytes (3) and the function of B lymphocytes (4). MSCs are not recognized by alloreactive T cells in vitro (5) and exert immunosuppressive effects regardless of HLA and species boundaries (6). A specific mechanism that could explain these effects has not been defined.…”

mentioning

confidence: 99%

Treatment of severe progressive systemic sclerosis with transplantation of mesenchymal stromal cells from allogeneic related donors: Report of five cases

Keyszer¹,

Christopeit²,

Fick³

et al. 2011

Arthritis & Rheumatism

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Mesenchymal stem cells distribute to a wide range of tissues following systemic infusion into nonhuman primates

Cited by 665 publications

References 17 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

Immunoregulatory function of mesenchymal stem cells

Treatment of severe progressive systemic sclerosis with transplantation of mesenchymal stromal cells from allogeneic related donors: Report of five cases

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