scholarly journals Alveolar Differentiation Potency of Human Distal Airway Stem Cells Is Associated with Pulmonary Pathological Conditions

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Yujia Wang ◽  
Yi Lu ◽  
Yingchuan Wu ◽  
Yufen Sun ◽  
Yueqing Zhou ◽  
...  

Background. This study is aimed at characterizing the human distal airway stem cells (DASCs) and assessing their therapeutic potential in patients with chronic, degenerative lung diseases. These findings will provide a comprehensive understanding for further clinical applications utilizing autologous airway stem cells as therapeutic intervention in respiratory diseases. Methods. DASCs were isolated from healthy subjects or patients diagnosed with bronchiectasis, chronic obstructive pulmonary diseases (COPD), or interstitial lung disease (ILD). Differentiation capacity, a key property of the stem cells, was studied using a novel monolayer differentiation system. The differentiated cells were evaluated for alveolar and bronchial cell marker expression, and the quantified expression level of differentiated cells was further examined for their relationship with age and pulmonary function of the subjects. Results and Conclusions. Differentiation of DASCs and tracheal stem cells (TSCs) yielded an alveolus-like structure and a tube-shaped structure, respectively, with distinct marker gene expression. Additionally, single-cell-derived clones showed diverse differentiation fates, even if the clones arise from identical or different individuals. More importantly, the alveolar differentiation potency was higher in DASCs derived from patients than from healthy people. The differentiation efficiency of DASCs also correlates with age in patients with bronchiectasis and ILD.

2009 ◽  
Vol 21 (1) ◽  
pp. 241
Author(s):  
M. T. Zhao ◽  
C. S. Isom ◽  
J. G. Zhao ◽  
Y. H. Hao ◽  
J. Ross ◽  
...  

Recently neural crest derived multipotent progenitors from skin have attracted much attention as the skin may provide an accessible, autologous source of stem cells available with therapeutic potential (Toma JG et al. 2001 Nat. Cell Biol. 3, 778–784). The multipotent property of stem cells could be tracked back to the expression of specific marker genes that are exclusively expressed in multipotent stem cells rather than any other types of differentiated cells. Here we demonstrate the property of multipotency and neural crest origin of porcine GFP-transgenic skin derived progenitors (termed pSKP) in vitro by marker gene expression analysis. The pSKP cells were isolated from the back skin of GFP transgenic fetuses by serum-free selection culture in the presence of EGF (20 ng mL–1) and bFGF (40 ng mL–1), and developed into spheres in 1–2 weeks (Dyce PW et al. 2004 Biochem. Biophy. Res. Commun. 316, 651–658). Three groups of RT-PCR primers were used on total RNA from purified pSKP cells: pluripotency related genes (Oct4, Sox2, Nanog, Stat3), neural crest marker genes (p75NGFR, Slug, Twist, Pax3, Sox9, Sox10) and lineage specific genes (GFAP, tubulin β-III, leptin). Expression of both pluripotency related genes and neural crest marker genes were detected in undifferentiated pSKP cells. In addition, transcripts for fibronectin, vimentin and nestin (neural stem cell marker) were also present. The percentage of positive cells for Oct4, fibronection and vimentin were 12.3%, 67.9% and 53.7% respectively. Differentiation assays showed the appearance of tubulin β-III positive (39.4%) and GFAP-positive (42.6%) cells in cultures by immunocytochemistry, which share the characteristics of neurons and glial cells, respectively. Thus, we confirm the multiple lineage potentials and neural crest origin of pSKP cells in the level of marker gene expression. This work was funded by National Institutes of Health National Center for Research Resources RR013438.


2014 ◽  
Author(s):  
Stefan Siebert ◽  
Freya E. Goetz ◽  
Samuel H. Church ◽  
Pathikrit Bhattacharyya ◽  
Felipe Zapata ◽  
...  

Background: Siphonophores (Hydrozoa) have unparalleled colony-level complexity, precision of colony organization, and functional specialization between zooids (i.e., the units that make up colonies). Previous work has shown that, unlike other colonial animals, most growth in siphonophores is restricted to one or two well-defined growth zones that are the sites of both elongation and zooid budding. It remained unknown, however, how this unique colony growth and development is realized at the cellular level. Results: To understand the colony-level growth and development of siphonophores at the cellular level, we characterize the distribution of proliferating cells and interstitial stem cells (i-cells) in the siphonophore Nanomia bijuga. Within the colony we find that i-cells are present at the tip of the horn, the structure within the growth zone that gives rise to new zooids. They persist in the youngest zooid buds, but as each zooid matures i-cells become progressively restricted to specific regions within the zooids until they are mostly absent from the oldest zooids. I-cell marker-gene expression remained in gametogenic regions. I-cells are not found in the stem between maturing zooids. Domains of high cell proliferation include regions where i-cells can be found, but also include some areas without i-cells such as the stem within the growth zones. Cell proliferation in regions devoid of marker gene expression indicates the presence of mitotically active epithelial cell lineages and, potentially, progenitor cell populations. Conclusions: Restriction of stem cells to particular regions in the colony may play a major role in facilitating the precision of siphonophore growth, and also lead to a reduced developmental plasticity in other, typically older, parts of the colony. This helps explain why siphonophore colonies have such precise colony-level organization.


2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Cristina Quispe ◽  
Natália Cruz-Martins ◽  
Maria Letizia Manca ◽  
Maria Manconi ◽  
Oksana Sytar ◽  
...  

Due to its vast therapeutic potential, the plant-derived polyphenol curcumin is utilized in an ever-growing number of health-related applications. Here, we report the extraction methodologies, therapeutic properties, advantages and disadvantages linked to curcumin employment, and the new strategies addressed to improve its effectiveness by employing advanced nanocarriers. The emerging nanotechnology applications used to enhance CUR bioavailability and its targeted delivery in specific pathological conditions are collected and discussed. In particular, new aspects concerning the main strategic nanocarriers employed for treating inflammation and oxidative stress-related diseases are reported and discussed, with specific emphasis on those topically employed in conditions such as wounds, arthritis, or psoriasis and others used in pathologies such as bowel (colitis), neurodegenerative (Alzheimer’s or dementia), cardiovascular (atherosclerosis), and lung (asthma and chronic obstructive pulmonary disease) diseases. A brief overview of the relevant clinical trials is also included. We believe the review can provide the readers with an overview of the nanostrategies currently employed to improve CUR therapeutic applications in the highlighted pathological conditions.


Physiology ◽  
2020 ◽  
Vol 35 (2) ◽  
pp. 125-133 ◽  
Author(s):  
Sara Al-Ghadban ◽  
Bruce A. Bunnell

Adipose-derived stem cells (ASCs) can self-renew and differentiate along multiple cell lineages. ASCs are also potently anti-inflammatory due to their inherent ability to regulate the immune system by secreting anti-inflammatory cytokines and growth factors that play a crucial role in the pathology of many diseases, including multiple sclerosis, diabetes mellitus, Crohn’s, SLE, and graft-versus-host disease. The immunomodulatory effects and mechanisms of action of ASCs on pathological conditions are reviewed here.


2005 ◽  
Vol 108 (4) ◽  
pp. 309-321 ◽  
Author(s):  
Zoë D. BURKE ◽  
David TOSH

Cell therapy means treating diseases with the body's own cells. The ability to produce differentiated cell types at will offers a compelling new approach to cell therapy and therefore for the treatment and cure of a plethora of clinical conditions, including diabetes, Parkinson's disease and cardiovascular disease. Until recently, it was thought that differentiated cells could only be produced from embryonic or adult stem cells. Although the results from stem cell studies have been encouraging, perhaps the most startling findings have been the recent observations that differentiated cell types can transdifferentiate (or convert) into a completely different phenotype. Harnessing transdifferentiated cells as a therapeutic modality will complement the use of embryonic and adult stem cells in the treatment of degenerative disorders. In this review, we will examine some examples of transdifferentiation, describe the theoretical and practical issues involved in transdifferentiation research and comment on the long-term therapeutic possibilities.


2021 ◽  
Vol 23 (4) ◽  
pp. 566-574
Author(s):  
P. F. Muzychenko ◽  
Zh. M. Minchenko ◽  
T. I. Havrylenko ◽  
V. A. Cherniak ◽  
S. V. Demidov ◽  
...  

The aim – based on the analysis of the scientific literature focused on understanding the role of exosomes in the mechanisms of inflammation development and application of stem cells for cellular therapy in different pathological conditions, to identify and substantiate the prospects of using the exosomes as prognostic markers of a disease progression and application of their therapeutic potential in cardiovascular pathology. Global trends in the study of stem cells of different origins from the perspective of morphofunctional, molecular-genetic, cytogenetic, immunogenetic and cytological characteristics contribute significantly the development of regenerative medicine in the context of developing new methodological solutions for the use of stem cells and their components, particularly exosomes, for cell therapy of various pathological conditions. Studies show the indirect effect of exosomes on the immune response activation, coordination of cellular senescence processes and antigen presentation. There are also evidence of their impact on the structural and functional restoration of affected organs and blood vessels. The application potential of exosomes in practical medicine, particularly in the area of new approaches development to synthesize the newer biopharmaceuticals and as markers of multifactorial pathology course in conjunction with studies on the mechanisms of exosome involvement into immune processes is discussed. The study on the exosome-mediated mechanisms of inflammation in atherosclerosis is relevant, given the fact that their main physiological role is to implement the link between immunocompetent cells. Conclusions. Improving knowledge of the molecular biological mechanisms of the exosome influence on immunological processes in patients with cardiovascular pathology allows to expand the range of diagnostic and prognostic criteria for the formation of immuno-inflammatory reactions and endothelial dysfunction and to outline ways to personify the choice of therapeutic programs, which, in turn, can open approaches to develop fundamentally newer pharmaceuticals.


2019 ◽  
Vol 8 (9) ◽  
pp. 414-424 ◽  
Author(s):  
Jonas Schmalzl ◽  
Piet Plumhoff ◽  
Fabian Gilbert ◽  
Frank Gohlke ◽  
Christian Konrads ◽  
...  

Objectives The long head of the biceps (LHB) is often resected in shoulder surgery and could therefore serve as a cell source for tissue engineering approaches in the shoulder. However, whether it represents a suitable cell source for regenerative approaches, both in the inflamed and non-inflamed states, remains unclear. In the present study, inflamed and native human LHBs were comparatively characterized for features of regeneration. Methods In total, 22 resected LHB tendons were classified into inflamed samples (n = 11) and non-inflamed samples (n = 11). Proliferation potential and specific marker gene expression of primary LHB-derived cell cultures were analyzed. Multipotentiality, including osteogenic, adipogenic, chondrogenic, and tenogenic differentiation potential of both groups were compared under respective lineage-specific culture conditions. Results Inflammation does not seem to affect the proliferation rate of the isolated tendon-derived stem cells (TDSCs) and the tenogenic marker gene expression. Cells from both groups showed an equivalent osteogenic, adipogenic, chondrogenic and tenogenic differentiation potential in histology and real-time polymerase chain reaction (RT-PCR) analysis. Conclusion These results suggest that the LHB tendon might be a suitable cell source for regenerative approaches, both in inflamed and non-inflamed states. The LHB with and without tendinitis has been characterized as a novel source of TDSCs, which might facilitate treatment of degeneration and induction of regeneration in shoulder surgery. Cite this article: J. Schmalzl, P. Plumhoff, F. Gilbert, F. Gohlke, C. Konrads, U. Brunner, F. Jakob, R. Ebert, A. F. Steinert. Tendon-derived stem cells from the long head of the biceps tendon: Inflammation does not affect the regenerative potential. Bone Joint Res 2019;8:414–424. DOI: 10.1302/2046-3758.89.BJR-2018-0214.R2.


2005 ◽  
Vol 17 (2) ◽  
pp. 235 ◽  
Author(s):  
T.A.L. Brevini ◽  
F. Cillo ◽  
F. Gandolfi

Parthenogenetic embryonic stem cells have been obtained in mouse and in primates. However, it would be desirable to have an alternative experimental model that could be used to investigate the therapeutic potential of these cells. For this purpose, we generated parthenogenetic pig blastocysts from in vitro-matured oocytes activated by sequential exposure to 10 μM ionomycin for 5 min and 2 mM 6-DMAP for 3 h. Inner cell masses were isolated by immunosurgery and plated on mitotically inactivated STO fibroblast feeder layers in 4-well dishes. Cells were incubated in 5% CO2 at 37°C in low glucose DMEM/F10 medium supplemented with 1000 IU/mL of mouse recombinant LIF, 10% Knockout serum replacer (Gibco, Italy), and 5% FBS. Within 3 days, circular colonies with distinct margins of small round cells were observed on both substrates. When a colony enlarged enough to cover half or more of the well surface, cells were trypsinized in clumps never reaching single-cell suspension and passaged to a newly prepared well. The expression of a gene panel was examined by RT-PCR on a portion of the cells at each passage. Oct-4 and nanog were used as markers of pluripotency. Interferon-τ, α-Amilase, Bone Morphogenetic Protein-4, and Neurofilament were used as markers of trophectoderm, endoderm, mesoderm, and ectoderm differentiation respectively. After 4 passages, three colonies expressed Oct-4 and nanog and were negative for all four differentiation markers. Two colonies at the 5th and 7th passages maintained nanog but not Oct-4 expression, while remaining negative to all of the other genes. To induce the formation of embryoid bodies (EBs), cells were cultured in 50-μL droplets of medium without LIF. Initiation of differentiation of EBs was confirmed through both morphological examination and molecular analysis; mesodermal, ectodermal, and endodermal markers were all expressed by Day 9 of culture and Oct-4 and nanog expression was completely down-regulated. Interestingly, when EBs were returned to adherent culture conditions patches of differentiated cells tended to form, spontaneously differentiating into mesodermal, endodermal, or neuroectodermal cell monolayers. The present data suggest that it is possible to establish putative embryonic stem cells from pig parthenotes. Further studies are in progress to determine their ability to stably maintain the undifferentiated state. This work was supported by MIUR COFIN 20022074357 and Fondazione CARIPLO.


Author(s):  
Nur Shuhaidatul Sarmiza Abdul Halim ◽  
Badrul Hisham Yahaya ◽  
Jie Lian

: Stem cells derived from adipose tissues (ADSCs) have emerged as an ideal candidate for various models of respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), and acute respiratory distress syndrome. ADSCs have qualities that may make them better suited for treating inflammatory lung diseases than other MSCs. ADSCs show a lower senescence ratio, higher proliferative capacity and stability in terms of their genetic and morphology during long-term culture over bone marrow-derived mesenchymal stem cells (BMMSCs). With advanced research techniques, the advantageous effects of ADSCs seem limited to their ability to engraft, differentiate, and be related to their secretion of trophic factors. These trophic factors regulate the therapeutic and regenerative outcomes in various lung inflammatory diseases. Taken together, these particular qualities of ADSCs make them significantly relevant for clinical applications. This article discusses a recent advance of ADSCs biology and their translational application emphasizing their anti-inflammatory, immunomodulatory and regenerative properties particularly on lung inflammatory diseases. Besides, the relevant advancements made in the field, the regulatory aspects, and other challenges and obstacles will be highlighted.


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