relapse Improvement in renal functions & stopping degeneration of tissues [64] LSD & neurodegenerative diseases Genetics, tumor, age, and life style Allogenic UCSCs cells and biomaterial coaxed UCSCs organoids Organoids consisted of neuroblasts (GFAP+, Nestin+, and Ki67+) & SCs (OCT4+, SOC2+); UCSCs recover from MSE deficiency and improve cognition Treatment of Krabbe’s disease, hurler syndrome, MLD, TSD, ALD, AD, ALS, SCI, SCI, TBI, Parkinson's, stroke, and so forth [65–67] Cartilage and tendon injuries Accident Transplantation of UCB-SCs, UCB-SCs-HA gel HA gel factors promote regeneration of hyaline cartilage & tendons in wks time Recovery from tendons and cartilage injuries [68, 69] Hodgkin’s lymphoma Genetic and environmental Transplantation of UCSCs Second dose infection of allogenic UCSCs improves patients life by 30% Treatment of Hodgkin’s lymphoma and other cancers [10] Peritoneal fibrosis Long term renal dialysis and fibrosis WJ-SCs, transplantation by IP injection WJ-SCs prevent programmed cells death and peritoneal wall thickness Effective in treatment of encapsulating peritoneal fibrosis [70] International Journal of Cell Biology 5 Table 1: Continued. SCs Disease Factors causing disease Mode of stem cells application Physiological and mechanistic aspects of stem cells therapeutics Improvements in disease signatures & future use References BMSCs Anaemia and blood cancer Injury, genetics autoimmunity Two-step infusion of lymphoid and myeloid Haplo identical BMSCs can reconstruct immunity, which is major process for minority Treatment of aplastic anaemia & haematological malignancies [71] AIDS HIV1 infection Transplantation of HIV1 resistant CD4+ cells Anti-HIV1 CD4+ cells express HIV1 anti-RNA, which restrict HIV infection Treatment of AIDS as an alternative of antiretroviral [72, 73] Blood clotting disorders Lack of platelets Transplantation of megakaryocyte organoids GFs in silk sponge, microtubule 3D scaffolds mimic bone marrow Therapeutics of burns and blood clotting diseases [74, 75] Neurodegenerative diseases Accidents, age, trauma, and stroke Focal transplant of BMSCs with LA LA+BMSCs induce neovascularisation that directs microglia for colonization Treatment of neuronal damage disorders and cognitive restoration [76] Orodental deformities Trauma, disease, and birth defects Bone marrow derived stem & progenitor (TRC) CD14+ & CD90+ TRC accelerate alveolar jaw bone regeneration Regeneration of defects in oral bone, skin, and gum [77] Diaphragm abnormalities Accidents & birth defects Implantation of decellularized diaphragm BMSCs niche perfused hemidiaphragm has similar myography & spirometry Replacement therapy by donor derived niched diaphragm [8] iPSCs Eye defects Age, genetics, and birth defects iPSCs derived NPCs transplantation NPCs form 5-6 layers of photoreceptor nuclei, restoring visual acuity Treatment of ARMD and other age-related eye defects [78–80] Neurodegenerative disorders Accidents, age, trauma, and stroke iGABA-INs and cortical spheroid transplantation (iGABA-INs) secrete GABA; FOX1G cause ASD, spheroid mimics to brain ASD, Alzheimer's, seizer, and obstinate epilepsies treatment [81–84] Liver & lung diseases A1AD deficiency Transplantation of A1AD mutation corrected iPSCs A1AD is encoded by SERPINA1 in liver, and mutation leads to drugs sensitivity Treatment of COPD causing lungs and liver degeneration [85] Diabetes Life style and genetic factors iPSCs derived 𝛽-cells transplantation Skin to 𝛽-cells reprogramming phase through cDE & cPF requires GPs Treatment of T1DM and T2DM and insulin production [86] Lung degeneration Tuberculosis, cancer, and fibrosis Biomaterial coaxed iPSCs transplantation Miniature iPSCs lung resembles airways and alveoli, model drug testing Regeneration of lung tissue [87] SIDs and AIDS Age, genetic factors, and infection Transplantation of Oct4 and Nanog corrected iPSCs CRISPER-Cas9 generate iPSCs in single step; iPSCs-M 𝜙 resists HIV1 Immunotherapy of SIDs, HIV1, and other immune diseases [80, 88, 89] 6 International Journal of Cell Biology Egg Blastocyst Embryo Embryonic stem cells Diabetic treatment Regeneration of cardiac tissue Drug screening Regeneration of liver Differentiation COCO Cone cells ARMD treatment Hepatocytes Cardiomyocytes Chondrocytes PPCs Fibrin embedding Regeneration of cartilage RGC Glaucoma treatment Drug screening ESCs in regenerative medicine Pacemaker cells Restoration of heart rhythm . IVG Infertility treatment Therapeutic applications Therapeutic applications K2 + LA 𝛽-cells Figure 2: ESCs in regenerative medicine: ESCs, sourced from ICM of gastrula, have tremendous promises in regenerative medicine. These cells can differentiate into more than 200 types of cells representing three germ layers. With defined culture conditions, ESCs can be transformed into hepatocytes, retinal ganglion cells, chondrocytes, pancreatic progenitor cells, cone cells, cardiomyocytes, pacemaker cells, eggs, and sperms which can be used in regeneration of tissue and treatment of disease in tissue specific manner. and transdifferentiation processes [14] has been considered as critical regulatory switch for lineage commitment of ESCs. The diverse lineage commitment potential represents ESCs as ideal model for regenerative therapeutics of disease