Allogeneic transplantation of umbilical cord-derived mesenchymal stem cells for diffuse alveolar hemorrhage in systemic lupus erythematosus

Abstract

Umbilical cord-derived mesenchymal stem cell transplantation (UC-MSCT) has been proved to be effective in the treatment of systemic lupus erythematosus (SLE), based on animal experiments and clinical trials. Diffuse alveolar hemorrhage (DAH) is a rare complication of SLE with a high mortality usually over 50%. This study aimed to assess the efficacy of UC-MSCT in the treatment of SLE-associated DAH. Four SLE patients complicated with DAH, who underwent UC-MSCT, were included. Clinical changes before and after transplantation were assessed by measurements of hemoglobin, platelet level, oxygen saturation, and serological factors. High-resolution CT (HRCT) scans of the chest were performed to evaluate pulmonary manifestation. All the four patients showed dramatic improvements of their clinical manifestations. Hemoglobin was elevated after UC-MSCT and was sustained at a normal level 6 months after UC-MSCT in the four patients. Platelet level was upregulated in two patients who had thrombocytopenia at baseline. Oxygen saturation appeared to be normal at 1 month after UC-MSCT, and this result was confirmed by the HRCT scan of the chest. Serum albumin elevated to 3.5 g/dl 6 months after transplantation. Our findings suggest that UC-MSCT results in amelioration of oxygen saturation as well as hematological and serologic changes, which revealed that UC-MSCT could be applied as a salvage strategy for DAH patients.

Long-term cultured mesenchymal stem cells frequently develop genomic mutations but do not undergo malignant transformation

“…Deposition of qualified hUC-MSCs into cell banks therefore offers unique opportunities to speed up clinical translation of stem cells to 'cell medicine' for both autologous and allogeneic therapies. 7,15 Because of the low frequency of MSCs in human tissues, the primary MSCs must be expanded extensively in vitro to achieve the quantity necessary for therapeutic purposes. [29][30][31] Before our study, many authors have reported contradicting results concerning the ability of MSCs to undergo spontaneous malignant transformation, with some investigators demonstrating that MSCs become tumor cells spontaneously during in vitro cultivation, 18,19,32 and others reporting that MSCs do not develop any genetic mutations nor do they undergo transformation after long-term culture.…”

“…4,5 Cultured hUC-MSCs are being tested in several clinical trials (www.clinicaltrials.gov), and encouraging outcomes have been observed. [6][7][8] Because of the high frequency of genomic mutations during long-term passaging of ESCs and iPSCs, it is necessary to determine whether hUC-MSCs, such as ESCs and iPSCs, can be grown indefinitely in culture and undergo adaptive genetic changes during the long-term expansion.…”

Mesenchymal Stem Cells: Innovative Therapeutic Intervention for Autoimmune Rheumatic Diseases

“…Alveolar pulmonary hemorrhage and hematological abnormalities, that compromise life were treated with MSCs-UC and MSC-BM respectively. All patients presented improvement at one month [34,35]. From the same research group, Wang D et al [36] included 87 patients with refractory SLE with a risk of organ failure; these patients received an infusion of MSCs-BM of allogenic UC at a dose of 1× 10 6 cells/kg.…”

Mesenchymal stem cell therapy in horses: useful beyond orthopedic injuries?

“…As MSC have immunomodulating capacities, the imbalance of cytokine homeostasis, which is a prominent feature of SLE, might be modulated by the soluble factors produced by MSC upon their activation (Liang et al 2010). Indeed, treatment-refractory human SLE patients showed clinical and hematological improvements after allogeneic MSC transplantation (Sun et al 2009;Shi et al 2012). A similar approach as in these human clinical trials might prove beneficiary in horses suffering from SLE.…”