Engraftment of allogeneic mesenchymal stem cells in the bone marrow of a patient with severe idiopathic aplastic anemia improves stroma

We conducted a phase II, noncomparative, multicenter study to assess the efficacy and safety of allogeneic bone marrow‐derived mesenchymal stromal cells (BM‐MSCs) expanded in vitro for patients with aplastic anemia (AA) refractory to immunosuppressive therapy. Seventy‐four patients from seven centers received allogeneic BM‐MSCs at a dose of 1–2 × 106 cells/kg per week for 4 weeks. Responses were assessed at 0.5, 1, 2, 3, 6, 9, and 12 months after the first cells infusion. Patients with response at 1 month continued to receive four infusions. All patients were evaluable. The overall response rate was 28.4% (95% confidence interval, 19%–40%), with 6.8% complete response and 21.6% partial response. The median times to response of leukocytic, erythrocytic, and megakaryocytic linages were 19 (range, 11–29), 17 (range, 12–25), and 31 (range, 26–84) days, respectively. After median follow‐up of 17 months, overall survival was 87.8%. Seven patients developed transitory and mild headache and fever, but no other adverse events were observed. Antithymocyte globulin used in previous treatment and no activated infection throughout treatment were predictors for response. Allogeneic BM‐MSCs infusion is a feasible and effective treatment option for refractory AA. The trial was registered at www.clinicaltrials.gov as NCT00195624. Stem Cells Translational Medicine 2017;6:1569–1575

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“…In Fouillard et al's 13 report, bone marrow stroma of the patient improved but not hematopoiesis. This might be attributable to the sample size.…”

Section: Discussionmentioning

confidence: 91%

“…In 2003, Fouillard et al 13 reported a 68‐year‐old woman patient with SAA refractory to ATG and cyclosporine who was ineligible for allogeneic HSCT and received two infusions of allogeneic MSCs (allo‐MSCs). The bone marrow stroma of the patient improved, but improved hematopoiesis was not observed.…”

Section: Introductionmentioning

confidence: 99%

Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells Expanded In Vitro for Treatment of Aplastic Anemia: A Multicenter Phase II Trial

Pang

Xiao

Zhang

et al. 2017

Stem Cells Translational Medicine

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“…In addition, the dose of MSCs used in our study is similar to the MSC doses in other reports in the literature. [22][23][24][25] The results generated from our study can be used in future for establishment of the acceptable normal range of biological variability between MSC donors.…”

Section: Discussionmentioning

confidence: 99%

Transplantation of ex-vivo culture-expanded parental haploidentical mesenchymal stem cells to promote engraftment in pediatric recipients of unrelated donor umbilical cord blood: results of a phase I–II clinical trial

MacMillan

Blazar

DeFor

et al. 2008

Bone Marrow Transplant

240

168

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“…In patients, circulating MSCs drop to very low levels during the first hour after infusion [10]. A low level of MSC donor DNA has been identified in bone marrow in some patients [11,12]. We have examined autopsies and tissue samples of patients infused with Author contributions: L.v.B.…”

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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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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Engraftment of allogeneic mesenchymal stem cells in the bone marrow of a patient with severe idiopathic aplastic anemia improves stroma

Cited by 167 publications

References 8 publications

Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells Expanded In Vitro for Treatment of Aplastic Anemia: A Multicenter Phase II Trial

Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells Expanded In Vitro for Treatment of Aplastic Anemia: A Multicenter Phase II Trial

Transplantation of ex-vivo culture-expanded parental haploidentical mesenchymal stem cells to promote engraftment in pediatric recipients of unrelated donor umbilical cord blood: results of a phase I–II clinical trial

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

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