Table 2.
Studies on the therapeutic use of mesenchymal stem cells (MSCs) in aplastic anemia (AA), including clinical trials.
| Reference | N. of Patients | Main Findings |
|---|---|---|
| Infusion of MSCs in AA patients | ||
| Xiao Y., et al. 2012 | 18 | Sequential infusions of MSCs may improve hematopoiesis in AA. Six patients responded, 2 reached complete response at 3 months. |
| Clé D.V., et al. 2015 | 9 | Infusion of allogeneic MSCs in AA is safe but does not improve clinical hematologic response or engraft in recipient bone marrow. Two patients responded at 6 months. |
| Pang Y., et al. 2017 | 74 | In phase II prospective trial, MSC infusions evoked a response in 28.4% of cases (6.8% complete) in less than one month, with 88% OS at 17 months |
| Cotransplantation of MSCs and allogeneic hematopoietic stem cells | ||
| Xu L-X., et al. 2011 and 2014 | 5 | Haploidentical HSC transplant combined with umbilical cord MSC infusion allows engraftment with 12.5% incidence of severe GVHD and 25% mortality |
| Li X-H., et al. 2014 | 17 | Combined transplantation of haploidentical HSCs and MSCs on AA without an HLA-identical sibling was safe, reduced the incidence of severe GVHD (23.5%), and lead to good survival (88.2% and 76.5% at 3 and 6 months) |
| Liu Z., et al. 2017 | 44 | Cotransplantation of MSCs could reduce the risk of graft failure and severe GvHD in haploidentical setting. Acute GVHD occurred in 1/3 of cases and chronic one in 14.6%. The 12-month overall survival was 77.3% |
| Xu L., et al. 2018 | 24 | MSC and haploidentical HSC cotransplantation is effective and safe, with 50% acute GVHD, not related to gender, age, donor–recipient relations, and patient/donor pair. Patient/donor pair was significantly correlated with chronic GVHD. One year mortality was 20.8% |
| Zhao M., et al. 2019 | 25 | Peripheral blood HSCs from unrelated and related donor transplants and MSC infusions are effective and safe in AA. No severe acute GVHD and 21.7% chronic GVHD were registered. Overall survival was 84% at 22.9 months (median follow up). The 5-year overall survival rate after transplantation was 83.6% ± 7.5% |
| Wang H., et al. 2012 | 6 | Cotransplant of haploidentical HSCs and MSCs in children was effective and safe with no severe acute GVHD nor chronic GvHD, and 100% survival at 15 months |
| Wei W., et al. 2017 | 25 | Cotransplant of haploidentical HSCs and bone marrow-derived MSCs led to engraftment in 100% of cases (median time 12 days, range 11–22 days). Acute GvHD occurred in 64% cases (5 cases grades II–IV), and one patient died of grade IV skin, gut, and liver GvHD. Five cases developed chronic GVHD. |
| Wang Z., et al. 2019 | 35 | Cotransplant of haploidentical HSCs and MSCs led to hematopoietic reconstitution in 100% of cases (median time 14 days, range 10–22 days). Grade II/IV acute GvHD occurred in 26% cases and 23% developed chronic GVHD. The overall survival rate was 85.71%, with a median of 22 months (range 3.5–37 months). |
| Yue C., et al. 2018 | 6 | HLA-related donor HSCT and MSC infusion led to sustained, full donor chimerism, with a median time of myeloid/platelet engraftment of 13–15.5 days. One patient died of acute GVHD, and 5 patients were alive after a median follow-up of 21 months (range 17–40.5). |
| Hinden L., et al. 2019 | 26 | T-cell and NK-cell increased levels may predict a good response to HSCT and MSC cotransplantation. A better response was observed among patients who expressed low levels of IL-6 and IL-22, Th17-related cytokines, prior to therapy. |
| Other therapeutic mechanisms for MSCs | ||
| Liu L.L., et al. 2018 | - | Levamisole displayed a significant suppressive effect on the in-vitro adipogenic differentiation of bone marrow-derived MSCs from AA patients |
| Qu Y., et al. 2018 | - | Cyclosporin A suppressed adipogenic differentiation of MSCs by inhibiting interleukin-6 expression in AA |