Applications of stem cells and bioprinting for potential treatment of diabetes

Table 1 Results of some mesenchymal stem cells clinical trials in diabetes mellitus type 1[45]

Types	Routes of transplantation	Outcome
Human MSCs	Intravenously introduced to Non-obese diabetic/Severe combined immunodeficiency mice with total body irradiation or local abdominal or leg irradiation	Safe and efficient for the long-term treatment of severe complication after radiotherapy[46]
Umbilical cord derived MSCs	Injected directly into the pancreas	Improvement of metabolic control. Enhancement of islet engraftment and survival[42]
Bone marrow-derived MSC	Differentiated in vivo into functioning β-cells	Normalization of chronic hyperglycemia in a diabetic rat[47]
Human placenta ‑derived MSCs	Differentiated into islet-like cell clusters and transplanted into streptozocin-induced diabetic mice	Restoration of normoglycemia in diabetic mice[48]
Human umbilical cord blood derived MSCs	Differentiated into IPC through intravenous administration	Improvement in glycemic profiles, histological improvement of insulates[49]
Wharton's jelly and amniotic membrane derived MSCs	(1) Differentiated into IPC and transplanted into the liver; (2) Infected with PDX1 gene and differentiated to IPC; and (3) Differentiated into IPC and transplanted into the liver of STZ-induced diabetic rats	Expression of insulin Secretion of C-peptide; expression of pancreas-specific genes[49]; correspondence to high concentrations of glucose[50]; reduction of blood glucose levels after 4 wk of transplantation[51]

MSCs: Mesenchymal stem cells; IPC: Insulin-producing cells.

Table 2 Comparison of cell viabilities for ink jet based-, extrusion based- and laser assisted bioprinting[90]

3D bioprinting technique	Cell viability
Ink jet based bioprinting	80%-95 %[86,87]
Extrusion based bioprinting	89.46% ± 2.51%[88]
Laser assisted bioprinting	< 85%[89]

Table 3 Status of stem cell therapies and bioprinting in tissue repair and regeneration

Organs	Stem cell	Bioprinting
Heart	(1) Combination of Mesenchymal and c-kit (+) Cardiac stem cell[141]; and (2) Human embryonic stem cell–derived cardiomyocytes[142]	(1) 3D bioprinting approach for vascularized heart tissue engineering based on human umbilical vein endothelial cells and induced pluripotent stem cells-derived cardiomyocytes[143]; (2) 3D-printed patch composed of human cardiac-derived progenitor cells in a hyaluronic acid/gelatin (HA/gel) based matrix[144]; and (3) 3D endothelial bed was seeded with cardiomyocytes to generate aligned myocardium capable of spontaneous and synchronous contraction[145]
Blood vessels	(1) Endothelial cells derived from human embryonic stem cells[146]; and (2) Human Pluripotent Stem cells[147]	(1) Pluronic F127 was used as a sacrificial material for the formation of the vasculature through a multi-nozzle 3D bioprinting system[148]; and (2) Drop-on-demand bioprinting technique to generate in vitro blood vessel models[149]
Nerves	Mesenchymal stem cell[150,151]	(1) Novel technique for bioprinting of fibrin scaffolds by extruding fibrinogen solution into thrombin solution, utilizing hyaluronic acid (HA) and polyvinyl alcohol[152]; and Production of high-resolution 3D structures of polylactide-based materials via multi-photon polymerization and explores their use as neural tissue engineering scaffolds[153]
Eyes	(1) Embryonic stem cell[154]; and (2) Limbal stem-cell[155]	(1) Produced 3D cornea-mimicking tissues using human stem cells and laser-assisted bioprinting[156]; and (2) Physical and chemical signals through 3D-bioprinting of HA hydrogels and co-differentiation of retinal progenitor cells into photo receptors [157]
Kidneys	(1) Embryonic stem cell[158]; and (2) Human pluripotent stem cells[159,160]	Bioprinting method for creating 3D human renal proximal tubules in vitro that are fully embedded within an extracellular matrix[161]
Skin	Mesenchymal stem cells[102,162]	(1) Amniotic fluid-derived stem cells printed in a set of pressure-driven nozzles through hydrogel solutions[102]; (2) Novel bioink made of gelatin methacrylamide and collagen doped with tyrosinase is presented for the 3D bioprinting of living skin tissues[163]; and (3) 3D cell printing of in vitro stabilized skin model and in vivo pre-vascularized skin patch using tissue-specific extracellular matrix bioink[164]
Pancreas	(1) Embryonic stem cells[165]; and (2) Human embryonic stem cells[166,167]	(Not fully developed) reviews[168,169]
Brain	(1) Multipotent adult stem cells[170]; and (2) Endogenous neural stem cells[171]	(1) Method for fabricating human neural tissue by 3D printing human neural stem cells with a bioink, and subsequent gelation of the bioink for cell encapsulation[172]; and (2) 3D bioprinted glioma stem cell model, using modified porous gelatin/alginate/fibrinogen hydrogel that mimics the extracellular matrix[173]
Lungs	(1) Distal airway stem cell[174]; (2) Pluripotent stem cells[175]; and (3) Exogenous stem/progenitor cells[176]	Reviews[177,178]
Liver	(1) Mesenchymal stem cells[179]; and (2) Induced pluripotent stem cells-derived organ bud transplant[180]	(1) Human embryonic stem cells-derived hepatocyte-like cells were 3D printed using alginate hydrogel matrix[117]; (2) Development of a liver-on-a-chip platform for long-term culture of 3D human HepG2/C3A spheroids for drug toxicity assessment[104]; and (3) Liver tissue model conducive to hepatotoxicity testing was developed by bioprinting hepatic spheroids encapsulated in a hydrogel scaffold into a microfluidic device[181]