Stem cell therapy for insulin-dependent diabetes: Are we still on the road?

Table 1 The differences between human and mouse pancreatic embryogenesis

Differences	Mice	Human	Ref.
Morphological change	Early separation of foregut from notochord: e8.75	Delayed separation of foregut from notochord: 4-5 wpc	[58,59]
	Early formation of tip and trunk of pancreass: e14-e15	The tip and trunk pancreas form late: 6-8 wpc	[18,60,61]
	Late islet formation: Endocrine cells do not aggregate until birth to form islets	Islet formation is early: formation begins at 12 wpc	[62,63]
Expression of transcription factors	PDX1: Early expression, the current intestinal and notochord is still in contact with the expression	PDX1: Late expression, delayed until the foregut and notochord separated from each other	[58,59]
	NKX2.2: When it was confined to NGN3+ progenitor cells, it was widely expressed in mouse MPPs up to e13	NKX2.2: This expression does not appear until the cells have differentiated into endocrine lineage in human	[18,64]
	SOX17: It was not present in mouse pancreatic epithelial cells	SOX17: Markers specific to the endoderm of the human islet	[65]
Endocrine cell formation	α cells: e8.5	α cells: 8-9 wpc	[25,62,66]
	β cells: e10.5-e.12.5	β cells: 6 wpc
	δ cells: e14.5	δ cells: 10 wpc
	PP cells: e10.5-e.12.5	PP cells: 17 wpc

Table 2 Advantages and disadvantages of different types of stem cell therapy for diabetes

Cell types	Advantages	Disadvantages	Ref.
Embryonic stem cell	High degree of differentiation	ESCs is weak in directional differentiation and difficult to induce	[35,36]
		There are ethical issues: ESCs are usually allogeneic
		Teratoma, immune rejection and gene mutation may occur after transplantation
Induced pluripotent stem cell	IPSC technology does not use embryonic or egg cells, so ethical problems are less likely	At present, the differentiation scheme of induced pluripotent stem cells is not mature, and the induction efficiency is low, the stability is poor, and the cost is high	[39]
	Proprietary stem cells can be made from a patient's own cells, so there is less immune rejection	The use of virus vectors poses security problems
Adult stem cell	It is easy to achieve targeted differentiation, and some studies have shown that adult stem cells can be used to treat diabetes	The direction of differentiation is limited, not omnipotent	[43,44]
		After transplantation, the ability of induced differentiated cells to secrete insulin was usually lower than that of normal islet β cells, and the cell survival rate was also lower
		The efficiency of inducing differentiation at different stages is still low based on reprogramming and small molecule screening

IPSC: Induced pluripotent stem cell.