In medical research and clinical applications, safety is always our top priority. What is the safety of clinical infusion of mesenchymal stem cells, which has received much attention at present? Analysis from existing clinical studies shows that mesenchymal stem cell infusions are very safe, present no risk of infection or tumor, and have a very low probability of serious adverse events (SAE), much lower than that of immunosuppressive drugs. Today, we will analyze three sets of data together to understand the safety of MSCS transfusions.

The leading journal in stem cell research, with 600+ research articles, confirms the safety of MSCs infusion

The study by Chadwick C. Prodromos, Amir Barmada, and Joshua Sharan of the American Foundation for Regenerative Medicine is published in the 2023 issue of Current Stem Cell Research & Therapy, Volume 18, Issue 6. This is an influential journal in the field of stem cell research, and the research published has been rigorously peer-reviewed, and we have reason to believe in the authority of its findings.

The researchers used PubMed and Google Scholar to conduct an extensive scientific literature search for serious adverse events associated with intravenous mesenchymal stem cells (MSCs). Covering a wide range of diseases, This includes, but is not limited to, multiple sclerosis (MS), rheumatoid arthritis (RA), amyotrophic lateral sclerosis (ALS), ankylosing spondylitis, weakness, autism, cerebral palsy (CP), diabetes, idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), Crohn's disease, ulcerative colitis, lupus, Parkinson's disease, scleroderma, spine Myeloid injury (SCI) and traumatic brain injury (TBI) are a variety of diseases.

In addition, we focused specifically on serious adverse events associated with intravenous infusion of mesenchymal stem cells (MSCs). However, they excluded some conditions from the search, such as studies that used hematopoietic stem cells or genetically modified mesenchymal stem cells, or studies that combined MSCs with drugs or surgery, and studies that did not clearly define SAE. Only studies involving intravenous mesenchymal stem cell (MSCs) delivery routes were included.

Based on their search and selection, a total of 664 articles met the preliminary criteria. After further screening, 117 articles were included in the security review. Of these thousands of injection reports, only two SAEs from upper extremity thromboembolism were identified, and both were kidney patients in the same clinic with no sequelae and no pulmonary embolism.

This result gives us reason to believe that, when performed correctly, intravenous infusion of MSCs is extremely safe, with few reports of serious adverse events associated with its use. Because it means we can be more confident in using MSCs to treat a variety of diseases without having to worry too much about safety.

The Lancet: 55 Studies, 2696 Patients, MSCs Infusion Safe!

An article in the Lancet journal Eclinical Medicine summarizes the results of randomized clinical trials of mesenchymal stem cells from 2012 to 2019, which confirm the safety of mesenchymal stem cells.

In this paper, the author searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and other sources of randomized clinical trial information to explore several possible adverse reactions of mesenchymal stem cells in randomized clinical trials, including: (1) Acute adverse reactions within 24 hours; (2) infection; (3) thrombus; (4) Long-term events (mortality, malignancy).

In 2012, researchers reviewed the clinical adverse effects of mesenchymal stem cells prior to this date, including a total of eight randomized clinical trials with 369 patients, and identified fever as the only adverse event associated with MSC therapy. This study also added 47 randomized clinical studies (selected from 4,914 studies), for a total of 55 randomized clinical studies, including 2,696 patients, which were upgraded from the previous study.

The diseases under study include cardiovascular disease, neurological disease, kidney disease, liver disease, respiratory disease, endocrine disease, blood/tumor malignancy, immune deficiency, or inflammatory disease states. Cell sources include bone marrow, umbilical cord, fat, etc.

After comprehensive analysis, the risk of fever was significantly higher in the MSC group than in the control group (but decreased from the 2012 summary), the MSC group showed no significant increase in the risk of thrombosis/thromboembolic events compared with the control group, and the risk of death was significantly lower in the MSC group than in the control group. There was no significant increase in the risk of malignant tumor or ectopic tissue formation in MSC group.

Finally, no association was found between MSC therapy and the development of ‍‍ febrile acute infusion toxicity, infection, or malignancy. No association was found between MSC therapy and the development of thrombus. However, there was still a significant association between MSC treatment and fever. Of the 880 patients who reported fever in 19 randomized clinical trials, only 6 reported severe illness ‍. The authors say the review results could provide additional reassurance to researchers, clinicians, regulators, patients and families that MSCs is safe and reliable for use.

Meta-analysis reviews 15 years of clinical trials, 62 study results, 3546 patients, confirmed safety!

A meta-analysis published in Stem Cell Research&Therapy reviewed mesenchymal stem cell clinical trials over the past 15 years, identified all treatment-related adverse events associated with mesenchymal stem cell administration, and explored the safety of mesenchymal stem cells in clinical use, concluding that: Over 15 years, 3,546 patients and 62 clinical studies have confirmed the clinical safety of mesenchymal stem cells!

Only 2 of the studies were prospective non-randomized trials, and the rest were randomized controlled trials (RCTS) ranging from clinical trials Phase 1/2 to Phase 3. Among them, the number of clinical trials ranked first in Asia, and the number of studies was the largest. It was followed by North America and Europe. Follow-up ranged from 6 months to 2 years.

The mesenchymal stem cells used in these studies were mainly isolated from bone marrow, adipose tissue and umbilical cord. The injected dose ranges from 4×10^7 to 1.2×10^9 cells. MSC administration was not found to be strongly associated with major adverse events, such as vascular disease, urticaria/dermatitis, central nervous system disease, diarrhea, death, or infection.

The results of the study suggest that MSC therapy may cause a transient fever in patients that may occur within 48 hours. At the same time, MSC injection may also cause adverse events at the administration site. Regarding other minor adverse events, mesenchymal stem cells may be associated with insomnia, constipation, and fatigue. It was not associated with anemia, metabolic and nutritional disorders, nausea, seizures, and vomiting.

In conclusion, a number of clinical studies have been completed to confirm that MSC administration is strongly associated with transient fever and adverse events at the administration site, and is not associated with other adverse events.

Small series summary

With the continuous progress of technology, the safety of stem cells has been greatly guaranteed, and it is more and more applied in the treatment of clinical diseases, and has shown good therapeutic effect. We believe that with the deepening of the basic and clinical research of mesenchymal stem cells, it will certainly provide new therapeutic strategies for solving many "intractable diseases".