Mesenchymal stem cells modulate lung injury

Our plain-English summary of Mesenchymal stem cells modulate lung injury, by A.R. Brody, K.D. Salazar, S.M. Lankford (Proceedings of the American Thoracic Society, 2010).

The study

• Authors: A.R. Brody, K.D. Salazar, S.M. Lankford
• Journal: Proceedings of the American Thoracic Society
• Published: 2010;7(2):130-3
• Type of article: Review
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Mesenchymal stem cells (MSCs) have been shown to differentiate into a variety of mesenchymal cell types, including fibroblasts, myofibroblasts, osteoblasts, chondroblasts, adipocytes, and myoblasts, as well as epithelial cells. It has been shown that these cells can be recovered from bone marrow as well as umbilical cord blood, and they can be propagated, stored, and administered to animals and patients in clinical trials. It is clear that the cells engraft in the lung, and several laboratories have demonstrated an ameliorating effect in models of acute injury caused by LPS and in chronic lung injury induced by bleomycin and asbestos. However, it is not at all clear under what conditions these cells must be applied to provide an advantage and when using these cells might cause exacerbation of the lung injury. This brief review focuses on the biology of MSCs in vitro, how the cells have been used in some animal models, and the potential for their use in therapeutic strategies for diseases as diverse as lung cancer and interstitial fibrosis.

In plain English

This article was a brief review, given as a lecture, of research on mesenchymal stem cells (MSCs). These cells, from bone marrow or umbilical cord blood, can develop into several cell types. The authors discussed MSC biology, animal models of lung injury (including injury from LPS, bleomycin and asbestos), and possible clinical uses. In an earlier study from their laboratory, irradiated female rats received labeled MSCs by bone marrow transplant, then breathed an asbestos aerosol for 3 hours. Within 24 hours, significant numbers of labeled MSCs had moved into the developing asbestos-induced lesions. Two and a half weeks later, many had become macrophages, epithelial cells, fibroblasts or myofibroblasts. The authors noted no information existed on whether the stem cells changed those lesions. Their preliminary laboratory data showed that MSC culture fluid with activated TGF-b1 raised collagen gene (COL1A1) levels in a fibroblast cell line dose-dependently: 5- to 7-fold when concentrated 2.5-fold. An antibody to TGF-b1 blocked this effect. The authors concluded that whether MSCs ameliorate or worsen lung injury is an open question as laboratories move toward clinical trials.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Brief narrative review (Thomas A. Neff Lecture, Aspen Lung Conference) that also presents preliminary cell-culture data from the authors' laboratory
• Who was studied: No human study population. The authors' new laboratory data used conditioned media from bone marrow–derived MSCs and human umbilical cord blood MSCs, applied to a fibroblast cell line (16Lu) and to normal human lung fibroblasts (NHLF). The asbestos work described came from the authors' earlier rat study (reference 16).
• Exposure: In the earlier rat study the authors described, rats that had received a bone marrow transplant of GFP-labeled MSCs were exposed to an asbestos aerosol for 3 hours. The text does not name the fiber type. In the new laboratory data, fibroblasts were exposed to MSC-conditioned media, either latent or acid-activated.
• Main results:
  • In the authors' earlier rat study (reference 16, not new data in this article), significant numbers of labeled MSCs had migrated from the bone marrow into the developing asbestos-induced lesions within 24 hours after exposure.
  • In that same earlier study, two and a half weeks later many of the labeled MSCs in the lesions had differentiated into macrophages, alveolar epithelial cells, and interstitial fibroblasts and myofibroblasts.
  • New preliminary data: when the TGF-b1 in conditioned media from bone marrow or cord blood MSCs remained latent, it had no effect on collagen (COL1A1) levels in fibroblasts.
  • Acid activation of the conditioned media produced a significant dose-dependent increase in COL1A1 levels in fibroblasts.
  • Activated conditioned media from both MSC sources increased COL1A1 5- to 7-fold in 16Lu fibroblasts when concentrated 2.5-fold. Activated media raised pro-collagen gene expression in normal human lung fibroblasts to similar levels.
  • Adding an antibody against TGF-b1 abolished the increased collagen expression in fibroblasts treated with MSC-conditioned media. The authors took this to suggest that the effect works through a TGF-b1-dependent pathway.
• The authors' conclusion: The authors concluded that MSCs can differentiate into multiple cell types and engraft in the lung in several injury models. They also concluded that whether MSCs ameliorate or worsen various forms of lung injury is an unresolved question as laboratories move toward clinical trials.
• Limitations the authors state:
  • The authors state that it is not known whether the developing asbestos-induced lesions were changed in any way by the presence of the stem cells.
  • The authors describe their cell-culture findings as preliminary data.
  • The authors state that it is not known where and when MSCs should be used to provide effective therapy.

Topics

Medical terms in this study, explained in our Lexicon: STEM, Fibroblast, Clinical Trial, Lung Cancer, Interstitial Fibrosis.

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• Mitochondrial biogenesis in the pulmonary vasculature during inhalational lung injury and fibrosis — M.S. Carraway, H.B. Suliman, et al. (2008)
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