Cell Therapy

While the research industry is evolving fast, various cell types will be developed into treatments as novel cell therapeutics and studied for future applications. Human mesenchymal stem cells (MSCs) are widely used because of their interesting and promising results. These MSCs are multipotent cells that are capable of self-renewal and differentiation which can be isolated from bone marrow, umbilical cord, adipose tissues and others.

Cellular therapy (CT) background

Cellular Therapy (CT) is the transplantation of human cells to regenerate, replace, and repair damaged cells and tissues. Cell therapy practices date back to the 19th century and continue to expand on investigational and investment grounds. Cell therapy refers to the transfer of autologous or allogeneic cellular material into a patient for medical purposes. The year 1889 witnessed the first practices of cell therapy by Charles-Édouard Brown-Séquard—pioneer in hormone therapy at the time—who attempted to suppress the effects of aging using injections of animal testicle extracts. Today, cell therapy continues to evolve with ongoing investigations for clinical safety and efficacy, and with a global market size estimated to expand from USD 9.5 billion in 2021 to USD 23.0 billion in 2028.

Cell therapy includes stem cell- and non–stem cell-based, unicellular, and multicellular therapies, with different immunophenotypic profiles, isolation techniques, mechanisms of action, and regulatory levels. With new state-of-the-art technologies, innovative products, and limitless discoveries, a diverse number of cells may be used as a treatment for a wide variety of diseases and medical conditions- infectious, degenerative, autoimmune, cancer, and many more. Cellular Therapy started to play a vital role in the practice of medicine. Its technologies overlap with those of gene therapy, cancer vaccines, drug delivery, tissue engineering and regenerative medicine.

The aim of cellular therapy is to prevent and treat human diseases via administration of cells that have been treated, altered, or engineered ex vivo. Main applications include treatment of cardiac diseases, diabetes mellitus, bones and joints disease, genetic disorders, skin/soft tissue wounds, and cancer.

Stem cells can be found in an organism in embryos and adult cells; they are a type of unspecialized, self-renewable cells prepped to differentiate into any cell type and/or as many cell types. What dictates how many cell types stem cells can differentiate into is their developmental potency. Developmental potency represents a differentiation continuum starting with totipotency (i.e., highest differentiation potential; e.g., zygote) and dwindling to pluripotency (e.g., embryonic stem cells), multipotency (e.g., hematopoietic stem cells), oligopotent (e.g., myeloid stem cells), and unipotency (i.e., least differentiation potential; e.g., dermatophytes) 

Stem cells are the ideal cells to be used for cell therapy because of their two main properties: ability to replicate for long periods of time and to develop into different cell types. There are 3 major types of stem cells: 

The first two are naturally found, while iPSCs are produced in the laboratory.

Embryonic stem cells

Embryonic stem cells are derived from preimplantation embryos, which are capable of indefinite and undifferentiated proliferation. B Primate ES cells retain their ability to distinguish between trophoblast and embryonic endoderm, mesoderm, and ectoderm derivatives. Since these cells have the differentiation capacity to almost all cells or tissue, they have a good advantage to cure several diseases, including diabetes mellitus, Alzheimer’s, anemia and spinal cord injuries. 

Embryonic stem cells have an unlimited capacity for self-renewal as well as the potential to differentiate into every cell type in the body. These characteristics make hESC an extremely attractive cell source for regenerative medicine; derivatives may be used to repair damaged tissue or replace specific cells lost due to disease. Numerous hESC-based therapies have shown promise in animal models, and several of them are now in human clinical trials. 

Human embryonic stem cells  undifferentiated cells obtained from a 5-day pre-implantation embryo. Embryonic stem cells are pluripotent, whereby they can give rise to ALL kinds of cells in the human body.

 Induced Pluripotent Stem Cells (iPSCs) 

Induced pluripotent stem cells (iPSCs or iPS cells), are a type of pluripotent stem cell derived from adult somatic cells that have been genetically reprogrammed to an embryonic stem (ES) cell-like state through the forced expression of genes and factors important for maintaining the defining properties of ES cells. They are genetically engineered adult cells, programmed to behave like pluripotent embryonic stem cells.

The method of reprogramming somatic cells into iPS cells was first demonstrated that genomic integration and high expression of four factors, by virus, can reprogram fibroblast cells into iPS cells. iPS cells can be generated from fibroblasts by viral integration without c-Myc. Although these iPS cells showed reduced tumorigenicity in chimeras and progeny animal models, the reprogramming process is much slower, and efficiency is substantially reduced.

Various growth factors and chemical compounds have recently been found to improve the induction efficiency of iPS cells. Shi et al., demonstrated that small molecules, able to compensate for Sox2, could successfully reprogram mouse embryonic fibroblasts (MEF) into iPS cells. 

Strenuous efforts are being made to improve the reprogramming efficiency and to establish iPS cells with either substantially fewer or no genetic alterations. Besides reprogramming vectors and factors, the reprogramming efficiency is also affected by the origin of iPS cells.

Adult stem cells

Adult stem cells, also known as somatic stem cells, are undifferentiated cells found in different areas of the body. They differ from embryonic stem cells as they are multipotent, whereby they can only develop into specific types of cells. Adult stem cells include the following:

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