Recent advances in mesenchymal stem cells in the past six months (part three)

Posted by beauty33 on January 16th, 2020

7.J Crohns Colitis: long-term evaluation of mesenchymal stem cells in the treatment of Crohn's disease anal fistula

doi: 10.1093 / ecco-jcc / jjz116

Researchers from the Netherlands report that most patients with Crohn's disease who have received allogeneic bone marrow mesenchymal stem cells (bmMSCs) for anal fistula have not seen a relapse after four years.

Anal fistula occurs in about 25% of Crohn's disease patients, and even after treatment, only 37% of patients with complex anal fistula can achieve long-term cure. In previous studies, the research team demonstrated an 86% reduction in anal fistula in patients treated with 30,000,000bmMSC.

In this study, researchers evaluated the safety and efficacy of bmMSC therapy over four years in 13 patients treated with bmMSC and three patients treated with placebo. After 24 weeks of treatment, 67% of patients in the 10 million bmMSC treatment group had their fistulas closed, 86% in the 30 million bmMSC group, 29% in the 90 million group, and 33% in the placebo group. In 4 years, 75% of the 10 million bmMSC treated patients had clinical fistula healing, compared with 100% in the 30 million group and 20% in the 90 million group. None of the three patients in the placebo group healed partially or completely after 4 years. After evaluation by MRI, 67% of patients treated with bmMSC did not see neonatal fistula.

8. Dent Mater J: R.T.R® up-regulates the expression of cbfa1 induced by BMPs / SMAD and promotes osteogenic differentiation of bone marrow mesenchymal stem cells

doi: 10.4012 / dmj.2018-306

Study the isolation and culture of rat bone marrow mesenchymal stem cells (BMSCs), and use Bio-Oss® and R.T.R® materials to stimulate cell time. The alkaline phosphatase activity (ALP) and osteogenic differentiation-related indicators of each group were detected.

The results showed that the ability of Bio-Oss® and R.T.R® to promote the adhesion and proliferation of BMSCs increased with time, but the effect of R.T.R® at all time nodes was significantly higher than that of Bio-Oss® (p <0.05). Compared with Bio-Oss®, RTR® can promote BMSCs ALP activity and bone formation-related transcription factors bone morphogenetic protein-1 (BMP-1), Cbfa1 and osteoblastic marker genes ALP, type I collagen, osteopontin, expression of osteoadhesin and osteocalcin. Applying R.T.R® stimulation and down-regulating the expression of BMP-1 in BMSCs will inhibit the expression levels of Cbfa1, ALP, type I collagen, osteopontin, osteoadhesin and osteocalcin. R.T.R® can up-regulate the expression of BMP-1 and cbfa1 through the BMPs / SMAD signaling pathway, thereby promoting the expression levels and osteogenic differentiation of ALP, collagen I, osteopontin, osteoadhesin and osteocalcin.

9. Front Endocrinol: Chordin-Like 1 improves bone formation of bone marrow mesenchymal stem cells by enhancing BMP4-SMAD pathway

doi: 10.3389 / fendo.2019.00360

Chordin-like 1 (CHRDL1) is a secreted glycoprotein with a repeating cysteine-rich domain that binds to BMPs family ligands. Although it has been reported to play an important role in several systems, the exact role of CHRDL1 in osteogenesis of human bone marrow mesenchymal stem cells (hBMSCs) remains to be explored. This study aimed to investigate the role of CHRDL1 in osteogenic differentiation of hBMSCs and its potential molecular mechanism.

We found that CHRDL1 is up-regulated during hBMSCs osteogenesis, and rhBMP-4 administration can enhance CHRDL1 mRNA expression in a dose- and time-dependent manner. Knockdown of CHRDL1 did not affect hBMSCs proliferation, but inhibited BMP-4 dependent osteogenic differentiation, showing a decrease in mRNA expression levels and mineralization of osteogenic markers. In contrast, overexpression of CHRDL1 enhanced BMP-4-induced osteogenic differentiation of hBMSCs. In addition, by transplanting CHRDL1 gene-modified hBMSCs into nude mice, the defective femoral model showed higher new bone formation in the CHRDL1 overexpression group, but compared with the control group, the new in the CHRDL1 knockdown group Bone formation is lower. Consistent with the bone formation rate, the expression of CHRDL1 protein in the new bone formation regions of defective femurs in the CHRDL1 overexpression group increased, while the expression of CHRDL1 protein in the CHRDL1 knockdown group decreased compared to the control group. These indicate that CHRDL1 can promote osteoblast differentiation in vivo. In addition, mechanism studies have shown that CHRDL1 improves BMP-4-induced SMAD1 / 5/9 phosphorylation during the osteogenic differentiation of hBMSCs. In addition, BMP receptor type I inhibitor LDN-193189 can block the promotion of osteogenic differentiation and the activation of SMAD phosphorylation by CHRDL1.

In summary, our results show that CHRDL1 can promote osteogenic differentiation of hBMSCs by enhancing the activation of the BMP-4-SMAD1 / 5/9 pathway.

10.DCR: Analysis of the effects of adipose-derived mesenchymal stem cells on transanal sphincter crypt fistula

doi: 10.1097 / DCR.0000000000001333

Management of sphincteric crypt fistula remains a challenging issue, and mesenchymal stem cells are increasingly being used to treat perianal Crohn's disease, which provides new treatments for crypt fistula. The purpose of this study was to evaluate the safety and feasibility of using autologous mesenchymal stem cells to treat sphincter crypt fistulas.

Researchers screened male and female patients with sphincteric crypt fistulas. The main results were the safety, feasibility and effectiveness of mesenchymal stem cells in the treatment of patients with transsphincteric fistula.

Fifteen patients (8 females, average age 39.8 years) had transsphincteric fistulas and received mesenchymal stem cell treatment, followed up for 6 months. The median duration of disease at study entry was 3 years. No serious adverse events occurred. At 6 months, 3 patients had complete clinical healing, 8 had partial healing, and 4 had no clinical improvement. Imaging improved in 11 of the 15 patients.

It can be seen that autologous mesenchymal stem cells are safe and feasible for the treatment of sphincteric crypt fistula, and can make most patients fully or partially heal.