Recent trends in stem cell-based therapies and applications of artificial intelligence in regenerative medicine

Table 1 Summary of the clinical applications of different types of stem cells

Type of stem cell	Discovery time	Source	Advantages	Disadvantages	Clinical applications and prospects
Embryonic stem cells	mESC was first derived in 1980 by Evans and Kaufman[33] in the United Kingdom and Martin[34] in the United States. hESC was derived by Thomson et al[22] isolated from preimplantation blastocysts in 1998	ICM of embryo	Maximum potency and these cells have the potential to differentiate into any cell type of the body	Ethical concerns, risk of developing teratomas and tumors when these undifferentiated cells are implanted in vivo[44-47]	Spinal cord injury[54], macular degeneration[55-58], diabetes mellitus[59], ischemic heart disease[60]
Induced pluripotent stem cells	Induced pluripotent stem cells were first successfully generated by Takahashi and Yamanaka[64] in 2006	Fibroblast cells	These cells have the potential to differentiate into any cell type of the body. Overcomes the ethical concerns associated with embryonic stem cell research and clinical use. Organoid formation, and scope for personalized therapies	Genomic instability, carcinogenicity, immunological rejection	Macular degeneration[81] and Parkinson's disease[89]
Fetal stem cells	First isolated and cultured by John Gearhart and his team at the Johns Hopkins University School of Medicine in 1998[185]	Umbilical cord blood cells	High availability and reduced ethical concerns. Higher expansion rate. Possess osteogenic differentiation capabilities. Produce 2.5-fold more insulin than bone marrow derived cells	May not have adipogenic potential	Pancreatic islet cell generation in vitro. GvHD and systemic lupus erythematosus
		Amniotic fluid and placenta	Harvested with minimal invasiveness	No clinical trials have yet been conducted to assess the safety and effectiveness of these stem cells	Potential treatment for nerve injuries or neuronal degenerative diseases. Bladder regeneration, kidney, lung, heart, heart valve, diaphragm, bone, cartilage and blood vessel formation. Treatment for skin and ocular diseases, inflammatory bowel disease, lung injuries, cartilage defects, Duchenne muscular dystrophy, and stroke. Also used in peripheral nerve regeneration
Adult stem cells
Hematopoietic stem cells	First discovered for clinical use in mice in 1950’s and for clinical use in human in 1970[186,187]	Bone marrow	Multipotent cells	Risks of GvHD[110]. Risks of bloodstream infections caused by Gram-negative bacteria associated with allogeneic hematopoietic transplantation[111,112]. Hemorrhagic cystitis is another complication that has been reported in patients post hematopoietic stem cell transplantation[113]	Hematopoietic stem cell transplantation is used as therapy for several malignant and non-malignant disorders and autoimmune diseases. These cells are also used for the recovery of patients undergoing chemotherapy and radiotherapy[108]
Mesenchymal stem cells	First derived in 1970 and first report of clinical use in 2004[188]	Bone marrow	Potential to differentiate osteocytes, chondrocytes, adipocyte. Multipotentiality, immunomodulatory, anti-inflammatory, efficient homing capacity to injured sites, and minimum ethical issues[121-123]	Procurement of cells from this source is often painful and carries the risk of infection. Cell yield and differentiation potential is dependent on donor characteristics	Generation of pancreatic cells in vitro. Orthopedic conditions characterized by large bone defects, including articular cartilage repair and osteoarthritis, rheumatoid arthritis. BM-MSCs may also be used to treat non-unions, osteonecrosis of the femoral head and to promote growth in osteogenesis imperfecta. Potentially promising treatment for myocardial infarction, GvHD, systemic lupus erythematosus and multiple sclerosis
	First derived in 2001[185]	Adipose tissue isolated from liposuction, lipoplasty or lipectomy materials	This source results in the isolation of up to 500 times more stem cells than BM (5 × 103 cells from 1 g of AT). AT is accessible and abundant and secretes several angiogenic and antiapoptotic cytokines. The immunosuppressive effects of AT-MSCs are stronger than those of BM-MSCs	Cells from this source have inferior osteogenic and chondrogenic potential in comparison to BM-MSCs	Immunosuppressive GvHD therapy. Potential for cell-based therapy for radiculopathy, myocardial infarction, and neuropathic pain. Cosmetic/dermatological applications. Successfully used in the treatment of skeletal muscle-injuries, meniscus damage and tendon, rotator cuff and peripheral nerve regeneration

AT: Adipose tissue; AT-MSCs: Adipose-tissue derived mesenchymal stem cells; BM-MSCs: Bone marrow derived mesenchymal stem cells; GvDH: Graft vs host disease; hESC: Human embryonic stem cell; ICM: Inner cell mass; mESC: Mouse embryonic stem cell.