Using Cell-Based Strategies to Break the Link between Bronchopulmonary Dysplasia and the Development of Chronic Lung Disease in Later Life

Table 2

Studies examining the therapeutic effect of stem/progenitor cells in experimental models of adult chronic lung disease.

Experimental model	Therapeutic cell or product	Outcomes	Suggested mechanism	References
Cigarette smoke-induced adult lung injury	Bone marrow-derived MSCs, CdM, and BMCs (i.v.)	Restoration of alveolar structure; Increased pulmonary vascularity; Alleviation of pulmonary hypertension (by BMCs)	Paracrine mechanisms; Recruitment of BMCs by donor cells	[61]
Papain-induced adult lung injury	Bone marrow-derived MSCs (i.v.)	Improved alveolar structure	Engraftment and AT2 differentiation; Reduced alveolar epithelial apoptosis	[62]
Elastase-induced (i.t.) adult lung injury	Adipose tissue-derived MSCs (i.v. or cultured on PGA and transplanted after LVRS)	Restored gas exchange; Improved exercise tolerance	Growth factor release (HGF, VEGF)	[63, 64]
	Bone marrow-derived MSCs (i.t.)	Preservation of alveolar structure; Reduced inflammation; Upregulated growth factors	Paracrine mechanisms; HGF, EGF, and secretory leukocyte protease inhibitor secretion	[65]
	Lung resident multilineage progenitors Sca1^+CD45^−CD31^− (i.t.)	Improved survival; Attenuated alveolar damage	Immunomodulatory effects; Paracrine mechanisms	[76]
Bleomycin-induced adult lung injury (i.t.)	Human ESC-derived cells with AT2 epithelial phenotype (i.t.)	Improved body weight and survival; Improved arterial oxygen saturation; Decreased collagen deposition	Engraftment and AT1 differentiation; Paracrine mechanisms	[77]
	Bone marrow-derived MSCs (i.v.)	Reduced fibrosis and inflammation	IL-1 receptor antagonism; Decrease in NO metabolites, proinflammatory, and angiogenic cytokines	[66, 68, 70]
	hUC Wharton’s jelly-derived MSCs (i.v.)	Reduced fibrosis	Decreased TGF-β and TIMP activity; Increased MMP-2 activity	[67]
	Bone marrow-derived HSCs ± KGF overexpression (i.v.)	Reduced fibrosis	KGF-induced endogenous AT2 cell proliferation	[78]
Bleomycin-induced adult lung injury (i.n.)	hAECs (i.p.; i.v.)	Reduced fibrosis and collagen deposition; Improved lung function; Modulated inflammatory response	Anti-inflammatory effects	[74, 75]

Acronyms: AT1: alveolar epithelial type 1; AT2: alveolar epithelial type 2; BMC: bone marrow-derived cells; CdM: conditioned media; EGF: epidermal growth factor; EPC: endothelial progenitor cell; HGF: hepatocyte growth factor; HSC: hematopoietic stem cell; hAEC: human amnion epithelial cell; hUC: human umbilical cord; IL: interleukin; i.n.: intranasal; i.p.: intraperitoneal; i.t.: intratracheal; i.v.: intravenous; KGF: keratinocyte growth factor; LVRS: lung volume reduction surgery; MMP-2: matrix metalloproteinase 2; MSC: mesenchymal stem cell; NO: nitric oxide; PGA: polyglycolic acid; TGF-β: transforming growth factor-𝛽; TIMP: tissue inhibitor of metalloproteinase; VEGF: vascular endothelial growth factor.