Stem Cells Applications in Regenerative Medicine and Disease Therapeutics

Table 1

Application of stem cells in regenerative medicine: stem cells (ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs) have diverse applications in tissue regeneration and disease therapeutics.

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
ESCs	Spinal cord injuries	Infection, cancer, and accidents	ESCs transplantation to injury site	ESCs and secreted vasculogenic and neurogenic factor support tissue homing	Regeneration of spinal tissue and improved balance and sensation	[15]
	ARMD and glaucoma	Macular cones degeneration	ESCs-derived cones and RGCs transplantation to eye	COCO (activating TGF-β, BMP, and Wnt) & BRN3 (knock-in by CRISPER-Cas9) make ESCs become cones and RGCs form cells sheet & neuronal connection	Recovery from ARMD and macular defects & restoration of vision	[16, 17]
	Cardiovascular disease	Diabetes, drugs, genetic factor, and life style	ESCs-derived CMs & biomaterial coaxed ESCs	Cardiomyocytes express GCaMP3, secreting vasculogenic factors, and Tbox3 differentiates ESCs into SANPCs	Suppresses heart arrhythmias. CMs electrophysiologically integrate to heart as pacemaker	[18, 19, 28]
	Liver injuries	Toxins, drugs, genetic factors, and infection	Transplantation of ESCs-derived hepatocytes	ESCs-hepatocyte conversion is marked with expression of Cytp450, PXR, CYPA4&29, HNF4-α, and UGTA1; cells in transplant repopulate injured liver tissue	Regeneration of liver tissue can be used as model for screening of drugs	[20, 23, 24]
	Diabetes	Life style, heart defects, and genetics	Transplantation of ESCs-derived PPCs	Progenitors (CD24^+, CD49^+  &  CD133^+) differentiate into β-cells, secrete insulin, and express PDX1, GCK, and GLUT2	Improvement in glucose level and obesity can be used for treatment of T1DM and T2DM	[25, 26]
	Osteoarthritis	When cartilage tissue wears away	Transplantation of chondrocytes organoids	Chondrocytes (SOX9^+  & collagen-II^+) form cells aggregate & remain active for 12 wks at transplantation site	Regeneration of cartilage tissue can be used for treatment of injuries faced by athletes	[27]
TSPSCs	Diabetes	Life style and genetic factors	Transplantation of SCs derived PPCs organoid	PPCs need niche supported active FGF & Notch signalling to become β-cell	PPCs occupancy as β-cell can treat T1DM & T2DM	[25, 29, 30]
	Neurodental problems	Accidents, age, and genetic factors	Transplantation of DSPSCs as neurons	Neurons express nestin, GFAP, βIII-tubulin, and L-type Ca^2+ channels	Possible application in treatment of neurodental abnormalities	[31, 32]
	Acoustic problems	Age, noise, drugs, and infection	IESCs/IESCs-derived hair cells transplantation	γ-secretase shuts Notch by β-catenin & Atoh1 in lrg5^+IESCs to be hair cells	Cochlear regeneration leads to restoration of acoustic functions	[34, 35]
	Intestinal degeneration	Genetic factors and food borne infections	IPCs derived crypt-villi organoid transplantation	Mϕ, myofibroblasts, and bacteria signals IPCs to be crypt-villi organoid tissue	Regeneration of goblet mucosa can treat intestinal defects	[36–38]
	Corneal diseases	Burns, genetics, and inflammation	LPSCs transplantation to corneal tissue	LPSCs in transplant marked by ABCB5 differentiate into mature cornea	Regeneration of corneal tissue might treat multiple eye disease	[39, 40]
	Muscular deformities	Infection, drugs, and autoimmunity	Transplantation of PEG fibrinogen coaxed MABs	PDGF from MABs attract vasculogenic and neurogenic cells to transplant site	Muscle fibril regeneration; skeletal muscle defects treatment	[41, 42]
	Eye disease & retinopathy	Toxins, burns, and genetic factors	AdSCs intravitreal transplantation	AdSCs from healthy donor produce higher vasoprotective factors	Restoration of vascularisation, diabetic retinopathy treatment	[44, 45]
	Cardiac dysfunctions	Age, genetic factors, and toxins	Systemic infusion of CA-AdSCs myocardium	CA-AdSCs to epithelium differentiation are superior to AdSCs	Regeneration of ischemic myocardium	[47, 48]
MSCs	Bladder deformities	Cystitis, cancer, and infection	Transplantation of BD-MSCs to bladder	BDMSCs (CD105^+, CD73^+, CD34^−, and CD45^−) with SIS heal bladder in 10 wks	Bladder regeneration from different origins MSCs	[50, 51]
	Dental problems	Infection, cancer age, and accidents	Transplants of EMSCs + DSCs biopolymer tissue	EMSC-DSCs and vasculogenic factors in biopolymer give rise to mature teeth units	Regeneration of oral tissue and application in periodontics	[31, 52]
	Bone degeneration	Injuries and tumor autoimmunity	Coaxed MSCs transplant & MSCs infusion	Actin modelling by cytochalasin-D transforms MSCs into osteoblasts	Regeneration of bones, reduction in injury pain	[53–55]
	Muscle degeneration	Genetic factors and work stress	Coaxed MSCs transplant and MSCs infusion	Alginate gel protects MSCs from immune attack and controls GFs release	Regeneration of heart scar and muscle tissue in controlled way	[56, 57]
	Alopecia	Age, disease, and medicine use	Transplantation of GAG-coated DPCs	GAG coating mimics ECM microenvironment, promoting DPCs regeneration	Regeneration of hair follicle for treatment of alopecia	[58]
UCSCs	Congenital heart defects	Developmental errors	Transplantation of fibrin coaxed AFSCs	Addition of VEFG to PEG coaxed AFSCs promotes organogenesis	Regeneration of tissue repair for treatment of heart defects	[59, 60]
	Diabetes	Life style and genetic factors	WJ-SCs, transplantation, and intravenous injection	WJ-factors & Mϕ differentiate WJ-SCs into β-cells, decreasing IL6 & IL1β	Improvement in function of β-cells leads to treatment of diabetes	[7, 9, 61–63]
	SLE	Autoimmunity	Intravenous infusion of WJ-SCs	WJ-SCs decrease SLEDAI & BILAG; reinfusion protects from disease 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]
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-Mϕ resists HIV1	Immunotherapy of SIDs, HIV1, and other immune diseases	[80, 88, 89]