L-arginine: A promising metabolite in enhancing the protective effects of adipose-derived stem cells against ischemic pathologies

Table 1 Characteristics of adipose tissue-derived mesenchymal stem cells vs bone marrow-derived mesenchymal stem cells in the therapy of ischemic conditions

Characteristics	Mechanism of action	Ref.
Higher availability and abundance	Widely distributed and richer adipose tissue harvest	[33-35]
Higher proliferation capacity and enhanced survival under hypoxic stress	Upregulated expression of a variety of cellular signaling molecules (such as IGF-3, FGF-2, HIF-1α), and activation anti-apoptotic signaling pathway, etc.	[36-38]
Superior angiogenic potential	Higher secretion of pro-angiogenic factors (e.g., L-arginine, VEGF, FGF-2), enhanced MMP-2/9-mediated extracellular matrix remodeling	[40,46]
Enhanced paracrine activity	Release a broader spectrum of functional molecules (such as growth factors, chemokines and cytokines) through paracrine manner	[39,42,43]
Stronger immunosuppressive and anti-inflammatory effects	Higher production of immunosuppressive factors (such as IL-10, TGF-β, and PGE2), and promoting M2 macrophage polarization	[30,44,45]
Improved homing and engraftment	Highly expression of chemokine receptors (e.g., CXCR4 and CXCL12), enhancing cells migration and engraftment to ischemic tissues	[47,48]

IGF-3: Insulin-like growth factor-3; FGF-2: Fibroblast growth factor-2; HIF-1α: Hypoxia-inducible factor-1alpha; VEGF: Vascular endothelial growth factor; MMP: Matrix metalloproteinase; IL: Interleukin; TGF-β: Transforming growth factor beta; PGE2: Prostaglandin E2; CXCR4: C-X-C chemokine receptor type 4; CXCL12: C-X-C motif chemokine ligand 12.