Harnessing CD146-positive mesenchymal stromal cells for precision therapy in acute respiratory distress syndrome

Table 1 Comparative summary of CD146- and CD146+ mesenchymal stromal cells in acute respiratory distress syndrome

Parameter	CD146- MSCs	CD146+ MSCs	Literature-based clinical perspective	Ref.
Therapeutic efficacy in ARDS	Weaker effect; pulmonary edema persists, limited recovery	Superior effect; reduced pulmonary edema and improved systemic recovery	Therapeutic benefit depends on endothelial stabilization and inflammation resolution, both more effectively addressed by CD146+ cells	[1,5]
Immunomodulation	Weak Th1/Th17 suppression, limited Treg induction	Strong Th1/Th17 inhibition and marked Treg expansion	CD146+ MSCs exert deeper immune rebalancing, potentially extending use to autoimmune conditions	[5,9]
Paracrine signaling and secretory activity	Low production of HGF, PGE2, VEGF, Ang-1	High production of HGF, PGE2, VEGF, Ang-1	CD146 reflects a “high-secretory phenotype”, suggesting their EVs/secretome are also more potent	[5,6]
Endothelial barrier repair	Low VE-cadherin and ZO-1 expression	High VE-cadherin and ZO-1 expression	Barrier integrity is central in ARDS pathophysiology; CD146+ cells directly fortify endothelial junctions	[5]
Angiogenic potential	Poor tube formation	Strong tube formation	Vascular repair and perfusion recovery are essential for lung healing	[5,8]
Key signaling pathway	Weak NF-κB/COX-2 activation	Strong NF-κB/COX-2 activation	These pathways drive pro-regenerative factor release and may be pharmacologically targetable	[5,7]
Effect of culture conditions	Low CD146+ ratio	High CD146+ ratio (in YF medium)	Standardization of manufacturing conditions influences potency by altering CD146+ subpopulation frequency	[5,16,17]

Data are summarized from Zhang et al[5] and the related literature. MSCs: Mesenchymal stromal cells; ARDS: Acute respiratory distress syndrome; Th1: Type 1 helper T; Th17: Type 17 helper T; Treg: Regulatory T; HGF: Hepatocyte growth factor; PGE2: Prostaglandin E2; VEGF: Vascular endothelial growth factor; Ang-1: Angiopoietin-1; EVs: Extracellular vesicles; VE-cadherin: Vascular endothelial cadherin; ZO-1: Zonula occludens-1; NF-κB: Nuclear factor kappa-B; COX-2: Cyclooxygenase-2.