Advancing diabetes management: Exploring pancreatic beta-cell restoration’s potential and challenges

Table 2 Comparison of regenerative approaches for diabetes treatment

Regenerative approach	Mechanism of action	Advantages	Challenges	Examples	Ref.
Beta-cell regeneration and novel regenerative molecules	Stimulates proliferation, enhances function, and supports survival of existing beta cells	Potential for restoring endogenous insulin production and enhancing beta-cell mass	Reproducibility, safety concerns, and challenges in achieving efficient beta-cell proliferation	GLP-1 analogs, EGF, gastrin, Harmine (DYRK1A inhibitor)	[111,114-116,119]
Stem cell therapy	Differentiates stem cells into beta-like cells	Can potentially replace lost beta cells	Ethical concerns, risk of tumorigenesis, and immune rejection	hESCs, iPSCs	[89,124,125]
Gene editing	Corrects genetic defects in beta cells	Precise genetic modifications	Off-target effects, ethical concerns	CRISPR-Cas9, TALENs, ZFNs	[116,121,123]
Reprogramming molecules	Converts other pancreatic cell types into beta-like cells	Increases beta-cell mass	Efficiency and stability of reprogrammed cells remain areas of investigation	PDX1, NGN3, MAFA	[113]

CRISPR-Cas9: Clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9; DYRK1A: Dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A; EGF: Epidermal growth factor; GLP-1: Glucagon-like peptide 1; hESCs: Human embryonic stem cells; iPSCs: Induced pluripotent stem cells; MAFA: V-Maf musculoaponeurotic fibrosarcoma oncogene homolog A; NGN3: Neurogenin 3; PDX1: Pancreatic and duodenal homeobox 1; TALENs: Transcription activator-like effector nucleases; ZFNs: Zinc finger nucleases.