When Is an Alveolar Type 2 Cell an Alveolar Type 2 Cell? A Conundrum for Lung Stem Cell Biology and Regenerative Medicine

Michael F. Beers, Yuben Moodley

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Generating mature, differentiated, adult lung cells from pluripotent cells, such as induced pluripotent stem cells and embryonic stem cells, offers the hope of both generating disease-specific in vitro models and creating definitive and personalized therapies for a host of debilitating lung parenchymal and airway diseases. With the goal of advancing lung-regenerative medicine, several groups have developed and reported on protocols using defined media, coculture with mesenchymal components, or sequential treatments mimicking lung development, to obtain distal lung epithelial cells from stem cell precursors. However, there remains significant controversy about the degree of differentiation of these cells compared with their primary counterparts, coupled with a lack of consistency or uniformity in assessing the resultant phenotypes. Given the inevitable, exponential expansion of these approaches and the probable, but yet-to-emerge second and higher generation techniques to create such assets, we were prompted to pose the question, what makes a lung epithelial cell a lung epithelial cell? More specifically for this Perspective, we also posed the question, what are the minimum features that constitute an alveolar type (AT) 2 epithelial cell? In addressing this, we summarize a body of work spanning nearly five decades, amassed by a series of "lung epithelial cell biology pioneers,"which carefully describes well characterized molecular, functional, and morphological features critical for discriminately assessing an AT2 phenotype. Armed with this, we propose a series of core criteria to assist the field in confirming that cells obtained following a differentiation protocol are indeed mature and functional AT2 epithelial cells.

Original languageEnglish
Pages (from-to)18-27
Number of pages10
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume57
Issue number1
DOIs
Publication statusPublished - Jul 2017

Cite this

@article{c8dc70b3a0cc4f10af9ab4b84674461b,
title = "When Is an Alveolar Type 2 Cell an Alveolar Type 2 Cell? A Conundrum for Lung Stem Cell Biology and Regenerative Medicine",
abstract = "Generating mature, differentiated, adult lung cells from pluripotent cells, such as induced pluripotent stem cells and embryonic stem cells, offers the hope of both generating disease-specific in vitro models and creating definitive and personalized therapies for a host of debilitating lung parenchymal and airway diseases. With the goal of advancing lung-regenerative medicine, several groups have developed and reported on protocols using defined media, coculture with mesenchymal components, or sequential treatments mimicking lung development, to obtain distal lung epithelial cells from stem cell precursors. However, there remains significant controversy about the degree of differentiation of these cells compared with their primary counterparts, coupled with a lack of consistency or uniformity in assessing the resultant phenotypes. Given the inevitable, exponential expansion of these approaches and the probable, but yet-to-emerge second and higher generation techniques to create such assets, we were prompted to pose the question, what makes a lung epithelial cell a lung epithelial cell? More specifically for this Perspective, we also posed the question, what are the minimum features that constitute an alveolar type (AT) 2 epithelial cell? In addressing this, we summarize a body of work spanning nearly five decades, amassed by a series of {"}lung epithelial cell biology pioneers,{"}which carefully describes well characterized molecular, functional, and morphological features critical for discriminately assessing an AT2 phenotype. Armed with this, we propose a series of core criteria to assist the field in confirming that cells obtained following a differentiation protocol are indeed mature and functional AT2 epithelial cells.",
keywords = "type II pneumocyte, induced pleuripotent stem cell, embryonic stem cell, surfactant, lamellar body, SURFACTANT PROTEIN-B, RAT TYPE-II, PHENOTYPE IN-VITRO, IDIOPATHIC PULMONARY-FIBROSIS, RESPIRATORY-DISTRESS-SYNDROME, LAMELLAR BODY MEMBRANE, LONG-QT SYNDROME, A SP-A, EPITHELIAL-CELLS, BONE-MARROW",
author = "Beers, {Michael F.} and Yuben Moodley",
year = "2017",
month = "7",
doi = "10.1165/rcmb.2016-0426PS",
language = "English",
volume = "57",
pages = "18--27",
journal = "American Journal of Repiratory Cell and Molecular Biology",
issn = "1044-1549",
publisher = "AMER THORACIC SOC",
number = "1",

}

TY - JOUR

T1 - When Is an Alveolar Type 2 Cell an Alveolar Type 2 Cell? A Conundrum for Lung Stem Cell Biology and Regenerative Medicine

AU - Beers, Michael F.

AU - Moodley, Yuben

PY - 2017/7

Y1 - 2017/7

N2 - Generating mature, differentiated, adult lung cells from pluripotent cells, such as induced pluripotent stem cells and embryonic stem cells, offers the hope of both generating disease-specific in vitro models and creating definitive and personalized therapies for a host of debilitating lung parenchymal and airway diseases. With the goal of advancing lung-regenerative medicine, several groups have developed and reported on protocols using defined media, coculture with mesenchymal components, or sequential treatments mimicking lung development, to obtain distal lung epithelial cells from stem cell precursors. However, there remains significant controversy about the degree of differentiation of these cells compared with their primary counterparts, coupled with a lack of consistency or uniformity in assessing the resultant phenotypes. Given the inevitable, exponential expansion of these approaches and the probable, but yet-to-emerge second and higher generation techniques to create such assets, we were prompted to pose the question, what makes a lung epithelial cell a lung epithelial cell? More specifically for this Perspective, we also posed the question, what are the minimum features that constitute an alveolar type (AT) 2 epithelial cell? In addressing this, we summarize a body of work spanning nearly five decades, amassed by a series of "lung epithelial cell biology pioneers,"which carefully describes well characterized molecular, functional, and morphological features critical for discriminately assessing an AT2 phenotype. Armed with this, we propose a series of core criteria to assist the field in confirming that cells obtained following a differentiation protocol are indeed mature and functional AT2 epithelial cells.

AB - Generating mature, differentiated, adult lung cells from pluripotent cells, such as induced pluripotent stem cells and embryonic stem cells, offers the hope of both generating disease-specific in vitro models and creating definitive and personalized therapies for a host of debilitating lung parenchymal and airway diseases. With the goal of advancing lung-regenerative medicine, several groups have developed and reported on protocols using defined media, coculture with mesenchymal components, or sequential treatments mimicking lung development, to obtain distal lung epithelial cells from stem cell precursors. However, there remains significant controversy about the degree of differentiation of these cells compared with their primary counterparts, coupled with a lack of consistency or uniformity in assessing the resultant phenotypes. Given the inevitable, exponential expansion of these approaches and the probable, but yet-to-emerge second and higher generation techniques to create such assets, we were prompted to pose the question, what makes a lung epithelial cell a lung epithelial cell? More specifically for this Perspective, we also posed the question, what are the minimum features that constitute an alveolar type (AT) 2 epithelial cell? In addressing this, we summarize a body of work spanning nearly five decades, amassed by a series of "lung epithelial cell biology pioneers,"which carefully describes well characterized molecular, functional, and morphological features critical for discriminately assessing an AT2 phenotype. Armed with this, we propose a series of core criteria to assist the field in confirming that cells obtained following a differentiation protocol are indeed mature and functional AT2 epithelial cells.

KW - type II pneumocyte

KW - induced pleuripotent stem cell

KW - embryonic stem cell

KW - surfactant

KW - lamellar body

KW - SURFACTANT PROTEIN-B

KW - RAT TYPE-II

KW - PHENOTYPE IN-VITRO

KW - IDIOPATHIC PULMONARY-FIBROSIS

KW - RESPIRATORY-DISTRESS-SYNDROME

KW - LAMELLAR BODY MEMBRANE

KW - LONG-QT SYNDROME

KW - A SP-A

KW - EPITHELIAL-CELLS

KW - BONE-MARROW

U2 - 10.1165/rcmb.2016-0426PS

DO - 10.1165/rcmb.2016-0426PS

M3 - Article

VL - 57

SP - 18

EP - 27

JO - American Journal of Repiratory Cell and Molecular Biology

JF - American Journal of Repiratory Cell and Molecular Biology

SN - 1044-1549

IS - 1

ER -