Summary of Clinical Research Progress of Stem cells in Dongfang Hospital
Release Date:2024-06-11

Because stem cells have the potential of multi-directional differentiation and the ability of self-renewal, they can form primordial cells of various human organs and tissues, which are called "omnipotent cells" in medical circles. With the innovative development of science and technology, in recent years, speeding up the promotion of stem cell medical research, clinical transformation and industrialization has become the common goal of the medical and industrial circles. 

At present, Shanghai Oriental Hospital has two national platforms: the National Stem Cell Transformation Resource Bank (one of the two national stem cell banks) and the National Stem Cell Clinical Research Institute (one of the first 30 units in the country). There are Shanghai Zhangjiang Stem Cell Transformation Medicine Industrial Base, Shanghai Stem Cell Clinical Transformation Research Institute, Shanghai Stem Cell Clinical diagnosis and treatment Engineering Research Center, Shanghai Stem Cell preparation and quality Inspection Technical Service platform, Shanghai "Sixin" Economic Innovation Base, and Hainan Stem Cell Engineering Center (technical support) six provincial and ministerial platforms. Oriental Hospital prospectively laid out and created the first international leading stem cell research highland with the integration of "stem cell frontier basic research, preclinical research, clinical research, clinical transformation and application". 

So what other progress and research do they have in the field of stem cells? We have made the following summary according to the public reports on the Internet.

1.Clinical study of stem cell transplantation in the treatment of premature ovarian failure. 

Stem cells can improve the ability of ovarian reserve and cell proliferation, thus improving fertility. 

At present, Dongfang Hospital is preparing the clinical study of human amniotic epithelial mesenchymal stem cells in the treatment of premature ovarian failure.

2.Clinical study of stem cell transplantation in the treatment of osteoarthritis. 

Oriental Hospital carried out adipose MSC in the treatment of knee osteoarthritis; clinical design: double-blind, placebo-controlled single injection of adipose mesenchymal stem cells into both knees. 

Research progress: there have been 10 cases; put on record in Boao Lecheng advance area. 

A small sample study showed that the Recht standard of articular cartilage lesions in the intervention group was 0 cases relative to preoperative deterioration grade 1, accounting for 0% of the total number of cases. 

There were 2 cases unchanged, accounting for 20% of the total cases, 5 cases with grade 1 improvement, accounting for 50% of the total cases, and 3 cases with grade 2 improvement, accounting for 30% of the total cases.

3.Clinical study of stem cell transplantation in the treatment of Parkinson's disease. 

A clinical study of amniotic epithelial stem cells in the treatment of Parkinson's disease was carried out in Dongfang Hospital. 

Intervention: subscalp Ommaya capsule, 4 times intracerebroventricular injection of hAESCs, 5 × 10 ~ 7 cells per time. 

Research progress: completion of a study of 15 subjects. 

Safety analysis: there were no adverse events above CTCAE III level and III level, and special attention was paid to adverse events. 

Effectiveness analysis: 1-year follow-up observation, PD clinical scale evaluation showed varying degrees of improvement. 

PET- MR showed that the expression of dopamine transporter was higher than that before treatment, and the level of dopamine transporter in cerebrospinal fluid was higher than that before treatment at the 4th and 6th month. The level of dopamine in cerebrospinal fluid was higher than the baseline level after 4hAESCs treatment.

4.Stem cell anti-aging. 

Oriental Hospital conducted a randomized, double-blind, placebo-controlled study to observe the safety and efficacy of intravenous infusion of MSCs in the treatment of senile weakness (Clinicaltrial.gov registration number: NCT04314011). 

In this clinical observation study, 30 elderly patients with weakness were randomly assigned to either the MSCs group or the placebo group (0.9% saline) at 1:1. The subjects in the MSCs group received intravenous infusion of MSCs twice at a dose of 1 × 10 ^ 6 cells / kg (that is, 60 million cells per kilogram of body weight), once a month for a total of 2 times. 

The effectiveness results show that it can improve the quality of life, improve body function and reduce the level of inflammatory cytokines in elderly patients with weakness. The specific performance is as follows:

(1) improvement of quality of life: after the first administration, the physical health score (PCS) of SF-36 quality of life assessment scale in MSCs group was significantly better than that in placebo group, and the EQ-VAS score in MSCs group was significantly better than that in placebo group at 2 months (pause 0.023) and lasted until the end of visit (pause 0.002). 

(2) improvement of body function: there was significant difference in timing stand-up walking test (TUG), which improved continuously during the whole visit period (p < 0.05.After 6 months of follow-up, the time of 4-meter walking in MSCs group was 2.05s less than that in placebo group (p < 0.002). There was significant difference in grip strength between groups, and the increase of grip strength was greater in MSCs group (p < 0.002). 

(3) the level of inflammatory cytokines decreased: compared with placebo group, the levels of inflammatory cytokines (TNF- α, IL-17) in MSCs group decreased significantly at 6 months (pair0.034 and 0.033, respectively).

5.Treatment of heart failure with stem cells. 

"Human umbilical Cord Mesenchymal Stem Cell injection for Heart failure" has entered the phase I clinical trial. The main subjects are patients with severe chronic ischemic heart failure aged from 35 to 75 years old. stem cell injection is required during thoracotomy. The key to ensure the safety of the subjects is to overcome the risks of postoperative infection and bleeding. 

At this stage, the relevant subjects are from the Oriental Hospital, and will be recruited in conjunction with a number of third-class hospitals in the Yangtze River Delta to make a full scientific evaluation of clinical safety and effectiveness.

6.Stem cells in the treatment of ALS. 

The recruitment of Shize Biomedical Medicine and Shanghai Oriental Hospital "Clinical study of clinical iPSC-derived neural progenitor cells in the treatment of ALS" was officially launched on January 30, 2024.

7.Stem cell therapy for chronic obstructive pulmonary disease. 

In February 2024, Dongfang Hospital reported the results of the first phase clinical safety and efficacy study of the world's first p63 positive lung progenitor cell (P63 + LPC) transplantation, which provided a new idea for tissue regeneration and repair for all kinds of major respiratory diseases including COPD. The subjects were patients with II~IV COPD under the global diagnostic criteria for COPD (GOLD) and the diffusion function index (DLCO) was less than 80%. The vast majority of the subjects were severe or very severe COPD patients. A total of 20 subjects in the study completed the trial and follow-up, including 3 control subjects who received standard treatment (SOC) and 17 subjects who received standard therapy plus cell therapy. 

The subjects in the cell therapy group showed a significant improvement in DLCO (relative baseline DLCO change at 24 weeks: + 18.2%), compared with the control group (relative baseline DLCO change at 24 weeks:-17.4%) showed a statistically significant difference (p-value=0.008). After 12 weeks of cell therapy, the patients themselves also showed statistically significant differences, and up to 70.6% of the DLCO improvement of the patients in the cell treatment group reached the level of clinical benefit. In addition, the improvement trend of exercise ability (6-minute walking distance) and quality of life (SGRQ questionnaire) in the cell therapy group was also better than that in the control group, in which 66.7% of the subjects in the cell treatment group increased their 6-minute walking distance by more than 30 meters, while none in the control group reached this standard, showing a significant statistical difference (p-value=0.036).

8.Stem cell innovation technology-iPS cell. 

IPS cells reprogram terminally differentiated somatic cells into pluripotent stem cells by introducing specific transcription factors. After the differentiated cells are reversed under certain conditions, the process of returning to totipotent state, or forming embryonic stem cell lines, or further developing into new individuals is cell reprogramming. 

Dongfang Hospital has built a clinical-grade iPSC library with high frequency and homozygosity of HLA-A, B and DR, which can cover 60% of Chinese population. There were 288 strains in 103cases, covering 60% of the population with HLA matching.

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