Lung regeneration using amniotic fluid mesenchymal stem cells

Figures & data

Figure 1. The diagram depict human lung at embryonic and adult stages. During lung development (upper panel), the proximal progenitors expressing NKX2.1 + SOX2 + develops to produce the proximal cells lineages seen in the adult epithelium (lower panel). The distal tip progenitors represented as NKX2.1 + SOX9 + or NKX2.1 + FOXP2 + give rise to the stereotypical branching morphogenesis, and thereafter the respiratory epithelial cells. This image was adapted from [25] with copyright permission.

Table 1. Formation of anterior foregot endoderm using several factors and cocktails.

References	Year	Aim	Inhibition	Induction factors	Remark
Green et al. [34]	2011	Differentiation of hESCinto AFE	BMP and tgfβ using NOGGIN and SB431452	Wnt3a, FGF10, KGF, BMP4 and EGF	Sox2 was upregulated and CDX2 downregulated, generate up to 37% NKX2.1+
				+ RA	AFE enrichment Type-II ALVEOLAR CELL MARKER SP (SFTPC), and ciliated cell marker FOXJ1
Longmire et al. [35]	2012	Gene induction and modulation	NOGGIN and SB431452 alone		induce GFP expression in up to 21% of the cells
			NOGGIN and SB431452	Wnt3a, FGF10, KGF, BMP4, EGF and high conc. FGF2	upregulated both the thyroid and lung lineage genes expression
				Further differentiation of FGF10, FGF2, and mixture of dexamethasone, IBMX (DCI), FGF2, and cAMP.	downregulation of Nkx2.1 in about half of the cells
Longmire et al. [35]			SB431452 alone		10% of Nkx2.1
			BMP4, FGF2 and a GSK3 inhibitor		30% of Nkx2.1
			retinoic acid, BMP7, KGF, Wnt antagonism and MAPK/ERK inhibition		produced up to 18% Nkx2.1+ Sox2+ proximal progenitors

Table 2. Stepwise formation of lungs progenitor cells.

Procedure	Inferences	References
Ipsc or Esc + Activin A	Mesoendoderm	[34]
+ More Activin A	Definitive Endoderm	[36]
Inhibition Of Bmp and Tgf-B	Formation of anterior foregot endoderm (AFE) (Sox2 and FoxA2)	[34]
Wnt, FGF, EGF, KGF and BMP signalling	Formation of ventral AFE cells that express Nkx2.1	[37–41]
Treatment with FGF2 or FGF10 ligands	Promotes specification of lung progenitors, which express Nkx2.1, Sox2 and Sox9.	[42–46]

Firth AL, Dargitz CT, Qualls SJ, et al. Generation of multiciliated cells in functional airway epithelia from human induced pluripotent stem cells.. Proc Natl Acad Sci USA. 2014;111:E1723–E1730.

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Green MD, Chen A, Nostro M-C, et al. Generation of anterior foregut endoderm from human embryonic and induced pluripotent stem cells. Nat Biotechnol. 2011;29:267–272.

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Longmire TA, Ikonomou L, Hawkins F, et al. Efficient derivation of purified lung and thyroid progenitors from embryonic stem cells. Cell Stem Cell. 2012;10:398–411.

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