Programmed cell death in stem cell-based therapy: Mechanisms and clinical applications

Table 1 Summary of programmed cell deaths in stem cell-based therapy

Disease	SCs	Therapy models	Therapeutic effects	PCDs in SCs	Ref.
Myocardial infarction	MSCs	Canine; porcine; mice; human	Inducing cardiac regeneration; increasing angiogenesis; repair by differentiating into cardiomyocytes	Apoptosis, autophagy, pyroptosis	[46-48]
	iPSCs	Porcine; murine; rats; mice; non-human primates	Showing heart regeneration potential; regenerating the injured tissues; promoting a cardiomyogenic and angiogenic response	Apoptosis, autophagy, ferroptosis	[48,49]
	ESCs	Non-human primates	Showing heart regeneration potential; increasing angiogenic differentiation	Apoptosis, autophagy, pyroptosis	[48,50]
Intracerebral hemorrhage	MSCs	Rats; primates; human	Repairing via differentiating into neurons or neuron-like cells; promoting axonal regeneration, neurogenesis, and angiogenesis	Apoptosis, autophagy, pyroptosis	[51-54]
	NSCs	Mice, rats	Differentiating into neurons or glial cells; promoting neurogenesis and angiogenesis; promoting regeneration	Apoptosis, autophagy	[51,55-57]
	ESCs	Rats	Differentiating into neurons or glial cells; promoting neurogenesis and angiogenesis	Apoptosis, autophagy, pyroptosis	[51,58,59]
	iPSCs	Rats	Differentiating into neuroepithelium-like/neuroepithelioid SCs and neural cells; promoting neurogenesis and angiogenesis	Apoptosis, autophagy, ferroptosis	[51,60-62]
Corneal reconstruction	LSCs	Human	Regenerating the corneal epithelium; differentiating into cells of the corneal epithelium	Apoptosis.	[19]
	MSCs	Mice; rats; rabbits; human	Regenerating the corneal epithelium and corneal stroma; angiogenesis	Apoptosis, autophagy, pyroptosis	[63]
Neurodegenerative disorders of the gastrointestinal tract	ESCs	Mice	Differentiating into enteric neuronal and glial cells	Apoptosis, autophagy, pyroptosis	[20,64]
	iPSCs	Rats, mice	Differentiating into neural and glial cells	Apoptosis, autophagy, ferroptosis	[20,65]
	CNS-NSCs	Mice	Differentiating into neurons; regenerating and repairing ENS	Apoptosis, autophagy	[20,66,67]
	ENSCs	Mice; rats	Stimulating a local regenerative response; regenerating and repairing ENS; differentiating into new neurons	Apoptosis, autophagy	[20,68,69]
Diabetic cardiomyopathy	MSCs	Mice; rats	Promoting angiogenesis; regenerating tissues; differentiating into cardiomyocytes and vasculature cells	Apoptosis, autophagy, pyroptosis	[21,70]
	EPCs	Rats	Differentiating into endothelial cells to form new blood vessels and promoting neovascularization	Apoptosis	[70,71]
	CSCs/CPCs	Rats	Differentiating into newborn cardiomyocyte; promoting heart regeneration	Apoptosis	[70,72]
	iPSCs	Rats; mice	Attenuating oxidative stress and fibrosis; diminishing pro-oxidant expression and enhancing antioxidant (catalase and MnSOD) concentration; promoting heart regeneration	Apoptosis, autophagy, ferroptosis	[70,73]
Diabetic retinopathy	ASCs	Rats; mice	Promoting angiogenesis; improving ischemia; offering protection against nerve damage; differentiating into photoreceptor and glial-like cells in the retina	Apoptosis	[74-77]
	HSCs	Murine; rats	Promoting angiogenesis	Apoptosis, autophagy	[74,78]
	BM-MSCs	Murine; rats; mice	Differentiating into retinal glial cells; stimulating angiogenesis; promoting resident neural progenitors to regenerate neuro-retinal tissue	Apoptosis, autophagy, pyroptosis	[74,79,80]
	iPSCs	Rats; mice	Differentiating into cells expressing features of retinal pigment epithelial cells, retinal progenitor cells, and retinal ganglion cells, and slowing down retinal degeneration	Anti-apoptosis, autophagy, ferroptosis	[75,81]
Neurological disorders	NSCs	Mice, rats, monkeys, pigs, human	Differentiating into neurons and supporting glial cells; releasing angiogenic factors to promote local tissue regeneration	Apoptosis, autophagy	[82-85]
	HSCs	Human	Promoting cell survival; stimulating proliferation and migration of NSCs; inducing regeneration of damaged brain cells; promoting angiogenesis	Apoptosis, autophagy	[82,86]
	MSCs	Human	Promoting neuronal regeneration; promoting angiogenesis	Apoptosis, autophagy, pyroptosis	[82,86]
Diabetes	ESCs	Mice, rats	Differentiating into cluster of insulin producing beta cells	Apoptosis, autophagy, pyroptosis	[87-89]
	Hepatic and intestinal stem cells	Mice	Differentiating into beta cells in response to high glucose concentration	Apoptosis	[87,90]
	Spleen stem cells	Mice	Differentiating into insulin secreting beta cells; regenerating islet	Apoptosis	[87,91]
	HSCs	Mice	Differentiating into beta cells and vascular endothelial cells of the pancreas; inducing beta cell regeneration from the host cells residing in pancreas	Apoptosis, autophagy	[87,92]

SC: Stem cell; MSCs: Mesenchymal stem cells; NSCs: Neural stem cells; ESCs: Embryonic stem cells; iPSCs: Induced pluripotent stem cells; LSCs: Limbal stem cells; CNS-NSCs: CNS-derived NSCs; ENSCs: Enteric neural stem cells; CSCs/CPC: Cardiac stem/progenitor cells; ASCs: Adipose stem cells; HSCs: Hematopoietic stem cells; BM-MSCs: Bone marrow derived mesenchymal stem cells; ENS: Enteric nervous system; EPCs: Endothelial progenitor cells; PCD: Programmed cell death.