CYP3A4, and CYP2C9, which leads to differentiation of ESCs into hepatocytes; those are functionally similar to primary hepatocytes, for their ability to produce albumin and apolipoprotein B100 [20]. These hepatocytes 8 International Journal of Cell Biology MSCs/stromal cells in regenerative medicine Muscle degenerative disease treatment MSCs DPCS-LBL-GAG DPCs-EPCs co transplantation Hair reconstitution Treatment of acute liver failure cirrhosis and regeneration of bladder tissue Regeneration of cartilage Regeneration of bone tissue Ligament regeneration Heart scar repair after attack Transplantation to liver Healing of orthopedic injuries Transplantation and transdifferentiation to orthopedic tissues Muscle regeneration coculture leishmanial therapy CD73+, CD90+, CD105+ CD34−, CD45−, CD11b− CD14− , CD19 − , CD79a − coating + FGF2 Educated M𝜙 for AD-MSCs + M𝜙 Figure 4: MSCs in regenerative medicine: mesenchymal stem cells are CD73+, CD90+, CD105+, CD34−, CD45−, CD11b−, CD14−, CD19−, and CD79a− cells, also known as stromal cells. These bodily MSCs represented here do not account for MSCs of bone marrow and umbilical cord. Upon transplantation and transdifferentiation these bodily MSCs regenerate into cartilage, bones, and muscles tissue. Heart scar formed after heart attack and liver cirrhosis can be treated from MSCs. ECM coating provides the niche environment for MSCs to regenerate into hair follicle, stimulating hair growth. are excellent source for the endpoint screening of drugs for accurate prediction of clinical outcomes [20]. Generation of hepatic cells from ESCs can be achieved in multiple ways, as serum-free differentiation [21], chemical approaches [20, 22], and genetic transformation [23, 24]. These ESCs-derived hepatocytes are long lasting source for treatment of liver injuries and high throughput screening of drugs [20, 23, 24]. Transplantation of the inert biomaterial encapsulated hESCsderived pancreatic progenitors (CD24+, CD49+, and CD133+) differentiates into 𝛽-cells, minimizing high fat diet induced glycemic and obesity effects in mice [25] (Table 1). Addition of antidiabetic drugs into transdifferentiation regime can boost ESCs conservation into 𝛽-cells [25], which theoretically can cure T2DM permanently [25]. ESCs can be differentiated directly into insulin secreting 𝛽-cells (marked with GLUT2, INS1, GCK, and PDX1) which can be achieved through PDX1 mediated epigenetic reprogramming [26]. Globally, osteoarthritis affects millions of people and occurs when cartilage at joints wears away, causing stiffness of the joints. The available therapeutics for arthritis relieve symptoms but do not initiate reverse generation of cartilage. For young individuals and athletes replacement of joints is not feasible like old populations; in that case transplantation of stem cells represents an alternative for healing cartilage injuries [27]. Chondrocytes, the cartilage forming cells derived from hESC, embedded in fibrin gel effectively heal defective cartilage within 12 weeks, when transplanted to focal cartilage defects of knee joints in mice without any negative effect [27]. Transplanted chondrocytes form cell aggregates, positive for SOX9 and collagen II, and defined chondrocytes are active for more than 12 wks at transplantation site, advocating clinical suitability of chondrocytes for treatment of cartilage lesions [27]. The integrity of ESCs to integrate and differentiate into electrophysiologically active cells provides a means for natural regulation of heart rhythm as biological pacemaker. Coaxing of ESCs into inert biomaterial as well as propagation in defined culture conditions leads to transdifferentiation of ESCs to become sinoatrial node (SAN) pacemaker cells (PCs) [28]. Genomic incorporation TBox3 into ESCs ex vivo leads to generation of PCs-like cells; those express activated leukocyte cells adhesion molecules (ALCAM) and exhibit similarity to PCs for gene expression and immune International Journal of Cell Biology 9 Cord cells banking Umbilical arteries Wharton’s Jelly Amnion Umbilical cord blood Umbilical vein UCSCs in regenerative medicine Ex vivo expansion of UCSCs Intravenous delivery Pancreatic transplantation Treatment of diabetes Treatment of systematic lupus erythematosus HSCs Progenitors MSC UCSCs Infusion of UCSCs Treatment of Krabbe’s disease Ex vivo neurogenic organoid culture Application in neurodegenerative disease Treatment of neuroblastoma Treatment of spinal myelitis injection to pig knee Regeneration of tendons Injection of UCBMSCs to rotor cuff tendon tear-site Regeneration of hyaline cartilage of knee Treatment of severe congenital neutropenia Treatment of Hodgkin’s lymphoma Intraperitoneal transplantation Treatment of peritoneal fibrosis occurred long term dialysis 2x transplantation UCB-MSCs + HA Figure 5: UCSCs in regenerative medicine: umbilical cord, the readily available source of stem cells, has emerged as futuristic source for personalized stem cell therapy. Transplantation of UCSCs to Krabbe’s disease patients regenerates myelin tissue and recovers neuroblastoma patients through restoring tissue homeostasis. The UCSCs organoids are readily available tissue source for treatment of neurodegenerative disease. Peritoneal fibrosis caused by long term dialysis, tendon tissue degeneration, and defective