Umbilical cord mesenchymal stromal cells as critical COVID-19 adjuvant therapy: A randomized controlled trial.

One of the main causes of acute respiratory distress syndrome in coronavirus disease 2019 (COVID-19) is cytokine storm, although the exact cause is still unknown. Umbilical cord mesenchymal stromal cells (UC-MSCs) influence proinflammatory T-helper 2 (Th2 ) cells to shift to an anti-inflammatory agent. To investigate efficacy of UC-MSC administration as adjuvant therapy in critically ill patients with COVID-19, we conducted a double-blind, multicentered, randomized controlled trial at four COVID-19 referral hospitals in Jakarta, Indonesia. This study included 40 randomly allocated critically ill patients with COVID-19; 20 patients received an intravenous infusion of 1 × 106 /kg body weight UC-MSCs in 100 ml saline (0.9%) solution (SS) and 20 patients received 100 ml 0.9% SS as the control group. All patients received standard therapy. The primary outcome was measured by survival rate and/or length of ventilator usage. The secondary outcome was measured by clinical and laboratory improvement, with serious adverse events. Our study showed the survival rate in the UC-MSCs group was 2.5 times higher than that in the control group (P = .047), which is 10 patients and 4 patients in the UC-MSCs and control groups, respectively. In patients with comorbidities, UC-MSC administration increased the survival rate by 4.5 times compared with controls. The length of stay in the intensive care unit and ventilator usage were not statistically significant, and no adverse events were reported. The application of infusion UC-MSCs significantly decreased interleukin 6 in the recovered patients (P = .023). Therefore, application of intravenous UC-MSCs as adjuvant treatment for critically ill patients with COVID-19 increases the survival rate by modulating the immune system toward an anti-inflammatory state.

Allogeneic umbilical cord-derived mesenchymal stem cells for treating critical-sized bone defects: a translational study.

INTRODUCTION: The current 'gold-standard' treatment of critical-sized bone defects (CSBDs) is autografts; however, they have drawbacks including lack of massive bone source donor site morbidity, incomplete remodeling, and the risk of infection. One potential treatment for treating CSBDs is bone marrow-derived mesenchymal stem cells (BM-MSCs). Previously, there were no studies regarding the use of human umbilical cord-mesenchymal stem cells (hUC-MSCs) for treating BDs. We aim to investigate the use of allogeneic hUC-MSCs for treating CSBDs. METHOD: We included subjects who were diagnosed with non-union fracture with CSBDs who agreed to undergo hUC-MSCs implantation. All patients were given allogeneic hUC-MSCs. All MSCs were obtained and cultured using the multiple-harvest explant method. Subjects were evaluated functionally using the Lower Extremity Functional Scale (LEFS) and radiologically by volume defect reduction. RESULT: A total of seven (3 male, 4 female) subjects were recruited for this study. The subjects age ranged from 14 to 62 years. All seven subjects had increased LEFS during the end of the follow-up period, indicating improved functional ability. The follow-up period ranged from 12 to 36 months. One subject had wound dehiscence and infection, and two subjects developed partial union. CONCLUSION: Umbilical cord mesenchymal stem cells are a potential new treatment for CSBDs. Additional studies with larger samples and control groups are required to further investigate the safety and efficacy of umbilical cord-derived mesenchymal stem cells for treating CSBDs.

Evaluation of bone marrow-derived mesenchymal stem cell quality from patients with congenital pseudoarthrosis of the tibia.

BACKGROUND: The treatment of congenital pseudoarthrosis of the tibia (CPT) remains challenging in pediatric orthopedics due to the difficulties in bone union, continuous angulation, joint stiffness, and severe limb length discrepancy. Mesenchymal stem cells (MSCs) therapy offers a complementary approach to improve the conventional surgical treatments. Although the autologous MSC treatment shows a promising strategy to promote bone healing in CPT patients, the quality of MSCs from CPT patients has not been well studied. The purpose of this study is to investigate the quality of MSCs isolated from patients with CPT. METHODS: The bone marrow-derived MSCs from the fracture site and iliac crest of six CPT patients were isolated and compared. The cumulative population doubling level (cPDL), phenotype characteristics, and trilineage differentiation potency were observed to assess the quality of both MSCs. RESULTS: There were no significant differences of the MSCs derived from the fracture site and the MSCs from the iliac crest of the subjects, in terms of cPDL, phenotype characteristics, and trilineage differentiation potency (all p > 0.05). However, MSCs from the fracture site had a higher senescence tendency than those from the iliac crest. CONCLUSION: MSC quality is not the main reason for delayed bone regeneration in those with CPT. Thus, autologous MSC is a promising source for treating CPT patients.