Most of the clinical trials reached phase I and II, and very few of them reached phase III. MSCs are the most used stem cells in clinical trials, and MSCs have shown promising hope for patients in need of gene and cell therapies, and over 1220 clinical trials have been conducted over the world (keyword: mesenchymal stem cell at ). It is encouraged to work with MSC providers (or any other cells) that have an approved chemistry, manufacturing, and control for clinical trials, to facilitate the transition from preclinical to clinical trials but it is also important to determine the cell culture conditions in the preclinical phase that will be used in the clinical trials to ensure that the data obtained in the preclinical studies and the methodologies will be approved by the federal agencies. Positive and negative outcomes of stem cell therapy for animal studies and clinical trials can be related with the modification in the stem cells’ bioprocessing. The bioprocessing of any stem cells must be well planned and controlled, including the determination of the donors (inclusion/exclusion criteria), the methodology of isolation, the type of culture media, and the processes for the mass production. Typing the key words “bioprocessing, mesenchymal stem cells” in PubMed, there are only 160 publications referring to the large-scale production methodology of the mesenchymal stem cells. (c) An additional positive criterion is the large-scale manufacturing of the MSCs, which will provide enough cells for cell therapies.
MIANA KASSIS TRIAL
In the other hand, MSCs act also as immunomodulators, by reducing inflammatory activity, and were used as a racehorse cure with no immunoreaction, for the bone repair of rats, in a human trial for Crohn’s disease, and for perianal fistula, as outlined in a review publication. The absence or low immunogenicity of MSCs will allow their mass production, a better characterization, and the decrease of cost. This positive characteristic can be used for gene and cell therapy preclinical tests on animals before translational application, by using the MSCs that are planned to be utilized in the clinical trials (e.g., culture media, approved cells for clinical used by Federal Agencies). Human MSCs (hMSCs) were injected in different animals without any adverse events reported: mouse, rat, rabbit, zebrafish, swine, and dog, and as review for xenotransplantation of hMSCs. For the past 20 years, human MSCs were used in animal studies, with successes, on the basis of the low probabilities that the xenotransplantation of human cells in animals will trigger an inflammatory response and the human MSC rejection. In vitro studies showed that human bone marrow stem cells (BMSCs) are not recognized by T-lymphocytes but can suppress the proliferation of the T-lymphocyte. Functional MSCs do not express or express a very low level of HLA-DR (major histocompatibility complex class II, MHC II), meaning that MSCs have a lower immunogenicity than that of other cells. The activation of the HLA Class II leads to a rejection of transplanted cells or organs. In addition to this, the absence of HLA class II protein is a key factor, because MSCs could be used for allogeneic graft on patients, facilitating the use of MSCs in cell therapies. (b) MSCs have anti-inflammatory potential and immune-modulatory properties, and promote cell growth and tissue repair, through the secretion of cytokines and extracellular vesicles. MSCs curative properties and advantages can be divided in three different parts: However, there is always a risk that MSCs could transform into sarcoma, requiring a long-term follow-up on preclinical animal studies and clinical trials, up to 15 years based on the Food and Drug Administration guidelines (FDA). They can be cultured easily, and their stemness is characterized by the capacity of the MSC to self-renew and maintain the stemness properties, being passaged many times without karyotype alteration. They adhere quickly to the cell culture surface, and their morphology is fibroblastic. In the organism, the function of the MSC is to support the structure of the organs but also to generate cells of the specific organ when it is required. MSCs are pluripotent stem cells that were discovered around 30 years ago, and they can be isolated from bone marrow, adipose tissue, Wharton’s jelly, periosteum, villous chorion, fetus, and dental pulp, and there are no ethical issues. MSCs are very popular cells used in the research and over sixty-eight thousand publications involving the use of MSCs were published on PubMed, as of January 2021.
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