How the Fibrotic Lung Microenvironment Regulates Stem Cell Behavior: Immune Cues, Extracellular Matrix Remodeling, and Therapeutic Implications.

Distinct Roles for Matrix Metalloproteinases 2 and 9 in Embryonic Hematopoietic Stem Cell Emergence, Migration, and Niche Colonization.

Tercio del siglo XX, hay algunos relacionados con la mineria espanola. Charles Ledoux fue unos de los fundadores de la ?Sociedad Penarroya?, una de las mayores empresas de mineria y metalurgia del plomo, plata y cinc en Espana, Alexandre Pourcel y Adolphe Greiner participaron en el diseno y puesta en marcha de las principales plantas siderurgicas de Vizcaya, y Charles Barrois realizo un estudio fundamental de los terrenos del Paleozoico de Asturias. Estas medallas, realizadas en el estilo propio de la epoca, representan, ademas de una expresion artistica, un importante testimonio de historia minera.

The therapeutic role of mesenchymal stem cells (MSCs) in cases of amiodarone (AD) induced pulmonary fibrosis (PF) has not been well studied. Also, the period required by MSCs to attain full therapeutic effectiveness has not yet been assessed. We investigated the potential curative effect of bone marrow-derived MSCs (BM-MSCs) and conditioned media (CM) from BM-MSCs on AD induced PF by focusing on pulmonary epithelium injury and repair, and extracellular matrix (ECM) remodeling. We used 64 Wistar rats divided into eight groups: negative control group; PF group; three PF groups treated with BM-MSCs for 1, 2 or 4 months; and three PF groups treated with CM for 1, 2 and 4 months. Serum levels of Clara cell secretory protein (CC16) and keratinocyte growth factor (KGF) were measured. Gene expression of type I collagen (COL1A1) and connective tissue growth factor (CTGF) was evaluated in pulmonary tissue. Treatment of PF challenged rats with BM-MSCs or CM caused reduced CC16 levels, increased KGF levels, reduced expression of COL1A1 and CTGF, histological improvement following lung injury, and decreased collagen accumulation. Treatment with BM-MSCs exhibited greater amelioration of PF than CM. BM-MSCs or CM treatment for 2 and 4 months exhibited better resolution of fibrosis than treatment for 1 month. BM-MSCs are promising for treating PF due to their attenuation of ECM deposition in addition to alleviating pulmonary epithelium damage and initiating its repair.

Pulmonary fibrosis (PF) is a chronic, progressive, fibrotic interstitial disease of the lung with poor prognosis and without effective treatment currently. Data from previous coronavirus infections, such as the Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome, as well as current clinical evidence from the Coronavirus disease 2019 (COVID-19), support that SARS-CoV-2 infection may lead to PF, seriously impacting patient prognosis and quality of life. Therefore, effective prevention and treatment of PF will improve patient prognosis and reduce the overall social and economic burdens. Stem cells, especially mesenchymal stem cells (MSCs) have many great advantages, including migration to damaged lung tissue and secretion of various paracrine factors, thereby regulating the permeability of endothelial and epithelial cells, reducing inflammatory response, promoting tissue repair and inhibiting bacterial growth. Clinical trials of MSCs for the treatment of acute lung injury, PF and severe and critically ill COVID-19 are ongoing. The purpose of this study is to systematically review preclinical studies, explored the effectiveness of MSCs in the treatment of bleomycin (BLM)-induced pulmonary fibrosis and analyze the potential mechanism, combined with clinical trials of current MSCs for idiopathic pulmonary fibrosis (IPF) and COVID-19, so as to provide support for clinical research and transformation of MSCs. Searching PubMed and Embase (− 2021.4) identified a total of 36 preclinical studies of MSCs as treatment of BLM-induced acute lung injury and PF in rodent models. Most of the studies showed the MSCs treatment to reduce BLM-induced lung tissue inflammatory response, inflammatory cell infiltration, inflammatory cytokine expression, extracellular matrix production and collagen deposition, and to improve Ashcroft score. The results of present studies indicate that MSCs may serve as a potential therapeutic modality for the treatment of PF, including viral-induced PF and IPF.

What's in a Name?

MDS-Derived Stromal Cells Exhibit Altered Gene Expression and Support The Engraftment Of lin-CD34+CD38- Disease-Initiating Stem Cells In a Xenograft Model Of Lower Risk MDS

Stem cells (SCs) hold great potential for regenerative medicine, tissue engineering, and cell therapy. The clinical applications of SCs require both high quality and quantity of transplantable cells. However, during conventional in vitro expansion, SCs tend to lose properties that make them amenable for cell therapies. Extracellular matrix (ECM) serves an essential regulatory part in the growth, differentiation, and homeostasis of all cells in vivo, and when signals are transmitted to cells, they do not respond passively. Many cell types can remodel pericellular matrix to meet their specific needs. This reciprocal cell-ECM interaction is crucial for the conservation of cell and tissue functions and homeostasis. In vitro ECM remodeling also plays a key role in regulating the lineage fate of SCs. A deeper understanding of in vitro ECM remodeling may provide new perspectives for the maintenance of SC function. In this review, we critically examined three ways that cells can be used to influence the pericellular matrix: (1) exerting tensile force on the ECM, (2) secreting a variety of ECM proteins, and (3) degrading the surrounding matrix, and its impact on SC lineage fate. Finally, we describe the deficiencies of current studies and what needs to be done next to further understand the role of ECM remodeling in ex vivo SC cultures. Impact statement The effect of extracellular matrix (ECM) remodeling on physiological activities and disease progression has been extensively studied, but its effect on in vitro stem cell (SC) culture has received insufficient attention. More and more research has shown that in vitro ECM remodeling is critical for maintaining SCs function. This review will highlight how cells remodel ECM and the significance of ECM remodeling in ex vivo SC culture, as well as summarize the shortcomings of current research and what needs to be done next to further our understanding of the role of ECM remodeling in ex vivo SC culture.

Hydrogel from Acellular Porcine Adipose Tissue Accelerates Wound Healing by Inducing Intradermal Adipocyte Regeneration

Integrated proteomics and metabolomics reveal variations in pulmonary fibrosis development and the potential therapeutic effect of Shuangshen Pingfei formula

Human stromal (mesenchymal) stem cells (hMSC) represent a group of non-hematopoietic stem cells present in the bone marrow stroma and the stroma of other organs including subcutaneous adipose tissue, placenta, and muscles. They exhibit the characteristics of somatic stem cells of self-renewal and multi-lineage differentiation into mesoderm-type of cells, e.g., to osteoblasts, adipocytes, chondrocytes and possibly other cell types including hepatocytes and astrocytes. Due to their ease of culture and multipotentiality, hMSC are increasingly employed as a source for cells suitable for a number of clinical applications, e.g., non-healing bone fractures and defects and also non-skeletal degenerative diseases like heart failure. Currently, the numbers of clinical trials that employ MSC are increasing. However, several biological and biotechnological challenges need to be overcome to benefit from the full potential of hMSC. In this current review, we present some of the most important and recent advances in understanding of the biology of hMSC and their current and potential use in therapy.

Mesenchymal Stem Cells Stably Transduced with a Dominant-Negative Inhibitor of CCL2 Greatly Attenuate Bleomycin-Induced Lung Damage

Recent studies indicate that cardiac transfer of adult stem cells can have a favorable impact on tissue perfusion and contractile performance of the infarcted heart. Several cell sources are being explored in an effort to regenerate infarcted myocardium, including hematopoietic stem cells, endothelial progenitor cells, cardiac resident stem cells, bone marrow–derived multipotent stem cells, and mesenchymal stem cells (MSCs). Each of these cell types may have its own profile of advantages, limitations, and practicability issues in specific settings. Studies comparing the regenerative capacity of distinct cell populations are scarce. Most clinical investigators have therefore chosen a pragmatic approach by using unselected bone marrow cells that contain different stem cell populations. Basic scientists, by contrast, are focusing more on specific cell populations in a quest to understand the biological foundations of cell therapy and to identify the most promising stem cells for cardiac regeneration.1 See p 214 MSCs are a rare population of self-renewing, multipotent cells present in adult bone marrow. Although MSCs represent <0.01% of all nucleated bone marrow cells, they can be readily expanded in vitro. In defined culture media, MSCs differentiate into several mesenchymal cell lineages, including cardiomyocytes.2,3 When injected into normal adult myocardium, MSCs differentiate into cardiomyocyte-like cells with sarcomeric organization.4 In an earlier study in pigs with myocardial infarction (MI), MSCs grafted into the infarcted area were shown to express muscle-specific markers and to improve regional wall motion.5 Ease of isolation, high expansion capability, and cardiomyogenic potential have led to the proposition that MSCs may be a good choice for cell-based therapies of MI.6 In a report published in this issue of Circulation , Dai et al7 have …

Effects of exercise training and stem cell therapy on the left ventricle of infarcted rats

An in vitro culture platform to study the extracellular matrix remodeling potential of human mesenchymal stem cells

Global Challenges in Stem Cell Research and the Many Roads Ahead