Safety evaluation of P-MSC therapy
TNF-α, tumor necrosis, CLI, diarrhea, pruritus
DISEASE PROGRESSION, MINOR, ADVERSE EVENT, TUMOR NECROSIS
The MTD was not reached after P-MSC treatment, as no cases of DLT or AEs leading to discontinuation of P-MSC treatment were reported in this trial. Intramuscular injection of all doses of P-MSCs, including the maximum tested dose of 60 × 10Two patients experienced moderate post-injection diarrhea a day after cell therapy. In addition, two patients developed minor pruritus. The diarrhea improved on its own, and pruritus disappeared after one day of antihistamine therapy. There was one adverse event due to disease progression that was unrelated to the cell treatment; one patient received below-knee amputation of the treated leg three months after cell administration. During the follow-up phase, the physical evaluation and vital signs did not change from baseline.All patients underwent routine hematological and biochemical testing, both before and after cell treatment. The results demonstrated that the test improved over time. Among which FBs (fast blood sugar) showed a significant decrease (The immunological profiles (IL-1, IFN-γ, and TNF-α) (CD4, CD8, and CD25) of patients with CLI were evaluated before and 6 months after P-MSC administration in this study. The results demonstrated a statistically significant reduction in IL-1 and IFN-γ serum levels over a 6-month follow-up period after P-MSC therapy (Change in patients’ serum inflammatory cytokines levels on days 0 (baseline) and 6 months after the first infusion. Analysis of biomarkers on before (baseline) and 6 months after the first infusion demonstrated a significant reduction in IL-1, and interferon-γ (IFN-γ) in all patients with CLI. Serum levels of tumor necrosis factor alpha (TNF-α) decreased in four cases, but the differences were not statistically significant. *Patient samples were analyzed using flow cytometry for CD4, CD8, and CD25 markers before and after treatment with P-MSCs (Fig. Measured markers of CD4 and CD8 and CD25 on patients with CLI at screening and 6-month follow-up after P-MSC implantation