Fetal organ-derived mesenchymal progenitor cells have ability to support in vitro and in vivo hematopoiesis

AbstractThe terms MSC and MSCs have become the preferred acronym to describe a cell and a cell population of multipotential stem/progenitor cells commonly referred to as mesenchymal stem cells, multipotential stromal cells, mesenchymal stromal cells, and mesenchymal progenitor cells. The MSCs can differentiate to important lineages under defined conditions in vitro and in limited situations after implantation in vivo. MSCs were isolated and described about 30 years ago and now there are over 55,000 publications on MSCs readily available. Here, we have focused on human MSCs whenever possible. The MSCs have broad anti-inflammatory and immune-modulatory properties. At present, these provide the greatest focus of human MSCs in clinical testing; however, the properties of cultured MSCs in vitro suggest they can have broader applications. The medical utility of MSCs continues to be investigated in over 950 clinical trials. There has been much progress in understanding MSCs over the years, and there is a strong foundation for future scientific research and clinical applications, but also some important questions remain to be answered. Developing further methods to understand and unlock MSC potential through intracellular and intercellular signaling, biomedical engineering, delivery methods and patient selection should all provide substantial advancements in the coming years and greater clinical opportunities. The expansive and growing field of MSC research is teaching us basic human cell biology as well as how to use this type of cell for cellular therapy in a variety of clinical settings, and while much promise is evident, careful new work is still needed.

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Transcription factor Tlx1 marks a subset of lymphoid tissue organizer-like mesenchymal progenitor cells in the neonatal spleen

Scientific Reports ◽

10.1038/s41598-019-56984-w ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Yuta Ueno ◽

Keiko Fujisaki ◽

Shoko Hosoda ◽

Yusuke Amemiya ◽

Shogo Okazaki ◽

...

Keyword(s):

Transcription Factor ◽

Progenitor Cells ◽

Stromal Cells ◽

Lymphoid Tissue ◽

Stromal Cell ◽

Lineage Tracing ◽

Mesenchymal Progenitor Cells ◽

Reticular Cells

AbstractThe spleen is comprised of spatially distinct compartments whose functions, such as immune responses and removal of aged red blood cells, are tightly controlled by the non-hematopoietic stromal cells that provide regionally-restricted signals to properly activate hematopoietic cells residing in each area. However, information regarding the ontogeny and relationships of the different stromal cell types remains limited. Here we have used in vivo lineage tracing analysis and in vitro mesenchymal stromal cell assays and found that Tlx1, a transcription factor essential for embryonic spleen organogenesis, marks neonatal stromal cells that are selectively localized in the spleen and retain mesenchymal progenitor potential to differentiate into mature follicular dendritic cells, fibroblastic reticular cells and marginal reticular cells. Furthermore, by establishing a novel three-dimensional cell culture system that enables maintenance of Tlx1-expressing cells in vitro, we discovered that signals from the lymphotoxin β receptor and TNF receptor promote differentiation of these cells to express MAdCAM-1, CCL19 and CXCL13, representative functional molecules expressed by different subsets of mature stromal cells in the spleen. Taken together, these findings indicate that mesenchymal progenitor cells expressing Tlx1 are a subset of lymphoid tissue organizer-like cells selectively found in the neonatal spleen.

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A NEUROGENIC GENE EXPRESSION SIGNATURE SUPPORTS HUMAN THERMOGENIC ADIPOSE TISSUE DEVELOPMENT IN VIVO.

10.1101/2021.12.29.474474 ◽

2021 ◽

Author(s):

Javier Solivan-Rivera ◽

Zinger Yang Loureiro ◽

Tiffany DeSouza ◽

Anand Desai ◽

Qin Yang ◽

...

Keyword(s):

Adipose Tissue ◽

Progenitor Cells ◽

Gene Expression Signature ◽

Metabolic Effects ◽

Mesenchymal Progenitor Cells ◽

Thermogenic Adipocytes ◽

Mouse Adipocytes ◽

Species Specific

Human beige/brite thermogenic adipose tissue exerts beneficial metabolic effects and may be harnessed to improve metabolic health. To uncover mechanisms by which thermogenic adipose tissue is generated and maintained we developed a species-hybrid model in which human mesenchymal progenitor cells are induced in vitro to differentiate into white or thermogenic adipocytes and are then implanted into immuno-compromised mice. Upon implantation, thermogenic adipocytes form a more densely vascularized and innervated adipose tissue compared to non-thermogenic adipocytes. Mouse endothelial and stem/progenitor cells recruited by implanted human thermogenic adipocytes are also qualitatively different, with differentially expressed genes mapping predominantly to circadian rhythm pathways. We trace the formation of this enhanced neurovascular architecture to higher expression of a distinct set of genes directly associated with neurogenesis (THBS4, TNC, NTRK3 and SPARCL1), and to lower expression of genes associated with neurotransmitter degradation (MAOA, ACHE) by adipocytes in the developed tissue. Further analysis reveals that MAOA is abundant in human adipocytes but absent in mouse adipocytes, revealing species-specific mechanisms of neurotransmitter tone regulation. In summary, our work discovers specific neurogenic genes associated with development and maintenance of human thermogenic adipose tissue, reveals species-specific mechanisms of control of neurotransmitter tone, and suggests that targeting adipocyte MAOA may be a strategy for enhancing thermogenic adipose tissue activity in humans.

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Generation of functional human adipose tissue in mice from primed progenitor cells

10.1101/267427 ◽

2018 ◽

Cited By ~ 1

Author(s):

Raziel Rojas-Rodriguez ◽

Jorge Lujan-Hernandez ◽

So Yun Min ◽

Tiffany DeSouza ◽

Patrick Teebagy ◽

...

Keyword(s):

Adipose Tissue ◽

Progenitor Cells ◽

Adipogenic Differentiation ◽

Human Adipose Tissue ◽

Cyst Formation ◽

Mesenchymal Progenitor Cells ◽

Genes Encoding ◽

Immunocompromised Mice

AbstarctAdipose tissue is used extensively in reconstructive and regenerative therapies, but transplanted fat often undergoes inflammation and cell death, requiring further revision surgery. We report that functional human adipose tissue can be generated from mesenchymal progenitor cells in-vivo, providing an alternative approach to its therapeutic use. We leveraged previous findings that progenitor cells within the vasculature of human adipose tissue robustly proliferate in 3-dimensional culture under proangiogenic conditions. Implantation of these progenitor cells into immunocompromised mice results in differentiation towards non-adipocyte fates, incapable of generating a distinct tissue structure. However, priming of these progenitor cells in-vitro towards adipogenic differentiation results in formation of functional adipose tissue in-vivo. Mechanistically, priming induces the expression of genes encoding specific extracellular matrix and remodeling proteins, and induces extensive vascularization by host blood vessels. In comparison, grafts from adipose tissue obtained by liposuction undergo poor vascularization, adipocyte death, cyst formation, calcification and inefficient adiponectin secretion. Thus, primed mesenchymal adipose tissue progenitors reveal mechanisms of human adipose tissue development, and have potential to improve outcomes in reconstructive and regenerative medicine.

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In Vitro Characteristics and In Vivo Immunosuppressive Activity of Compact Bone-Derived Murine Mesenchymal Progenitor Cells

Stem Cells ◽

10.1634/stemcells.2005-0224 ◽

2006 ◽

Vol 24 (4) ◽

pp. 992-1000 ◽

Cited By ~ 73

Author(s):

Zikuan Guo ◽

Hong Li ◽

Xiusen Li ◽

Xiaodan Yu ◽

Hengxiang Wang ◽

...

Keyword(s):

Progenitor Cells ◽

Compact Bone ◽

Mesenchymal Progenitor Cells ◽

Immunosuppressive Activity

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In vitro and in vivo properties of distinct populations of amniotic fluid mesenchymal progenitor cells

Journal of Cellular and Molecular Medicine ◽

10.1111/j.1582-4934.2010.01180.x ◽

2011 ◽

Vol 15 (9) ◽

pp. 1896-1913 ◽

Cited By ~ 60

Author(s):

Maria G. Roubelakis ◽

Vasiliki Bitsika ◽

Dimitra Zagoura ◽

Ourania Trohatou ◽

Kalliopi I. Pappa ◽

...

Keyword(s):

Amniotic Fluid ◽

Progenitor Cells ◽

Mesenchymal Progenitor Cells

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Fibroin-Based Material from Natural Silk Can Be Associated with Alginate and Mesenchymal Progenitor Cells

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.396-398.437 ◽

2008 ◽

Vol 396-398 ◽

pp. 437-440 ◽

Cited By ~ 1

Author(s):

Leandra S. Baptista ◽

Carolina S.G. Pedrosa ◽

Karina R. da Silva ◽

Ronaldo J.F.C do Amaral ◽

Michele C.L. Kochem ◽

...

Keyword(s):

Stem Cell ◽

Progenitor Cells ◽

Silk Fibroin ◽

Core Protein ◽

Stem Cell Differentiation ◽

Stem Cell Markers ◽

Mesenchymal Progenitor Cells ◽

Freeze Dried

Silks are naturally occurring polymers and fibroin, its filament core protein, has been shown to support stem cell differentiation in vitro, and promote tissue repair in vivo. The aim of this study is to develop a biomaterial based on silk-fibroin fibers that can be associated with mesenchymal progenitor cells from human perichondrium in vitro, in order to promote auricular reconstruction in vivo. Silk-fibroin concentrate was dissolved with formic acid solution and freeze-dried in auricular moulds. Fibroin-based material was characterized by scanning electron microscopy and by cytotoxic assays. Perichondrium mesenchymal progenitor cells were characterized by flow cytometry. They expressed the standard mesenchymal stem cell markers, and were able to differentiate into several mesenchymal lineages in vitro. This fibroin-based material is a three-dimensional fibrillar scaffold, non-woven and biocompatible, which was also well integrated with alginate and mesenchymal cells.

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Bone Marrow Niches for Skeletal Progenitor Cells and their Inhabitants in Health and Disease

Current Stem Cell Research & Therapy ◽

10.2174/1574888x14666190123161447 ◽

2019 ◽

Vol 14 (4) ◽

pp. 305-319 ◽

Cited By ~ 4

Author(s):

Marietta Herrmann ◽

Franz Jakob

Keyword(s):

Bone Marrow ◽

Progenitor Cells ◽

Progenitor Cell ◽

Adult Stem Cells ◽

Current Knowledge ◽

Cell Populations ◽

Surface Markers ◽

Bone Marrow Niches

The bone marrow hosts skeletal progenitor cells which have most widely been referred to as Mesenchymal Stem or Stromal Cells (MSCs), a heterogeneous population of adult stem cells possessing the potential for self-renewal and multilineage differentiation. A consensus agreement on minimal criteria has been suggested to define MSCs in vitro, including adhesion to plastic, expression of typical surface markers and the ability to differentiate towards the adipogenic, osteogenic and chondrogenic lineages but they are critically discussed since the differentiation capability of cells could not always be confirmed by stringent assays in vivo. However, these in vitro characteristics have led to the notion that progenitor cell populations, similar to MSCs in bone marrow, reside in various tissues. MSCs are in the focus of numerous (pre)clinical studies on tissue regeneration and repair.Recent advances in terms of genetic animal models enabled a couple of studies targeting skeletal progenitor cells in vivo. Accordingly, different skeletal progenitor cell populations could be identified by the expression of surface markers including nestin and leptin receptor. While there are still issues with the identity of, and the overlap between different cell populations, these studies suggested that specific microenvironments, referred to as niches, host and maintain skeletal progenitor cells in the bone marrow. Dynamic mutual interactions through biological and physical cues between niche constituting cells and niche inhabitants control dormancy, symmetric and asymmetric cell division and lineage commitment. Niche constituting cells, inhabitant cells and their extracellular matrix are subject to influences of aging and disease e.g. via cellular modulators. Protective niches can be hijacked and abused by metastasizing tumor cells, and may even be adapted via mutual education. Here, we summarize the current knowledge on bone marrow skeletal progenitor cell niches in physiology and pathophysiology. We discuss the plasticity and dynamics of bone marrow niches as well as future perspectives of targeting niches for therapeutic strategies.

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Novel Identified Circular Transcript of RCAN2, circ-RCAN2, Shows Deviated Expression Pattern in Pig Reperfused Infarcted Myocardium and Hypoxic Porcine Cardiac Progenitor Cells In Vitro

International Journal of Molecular Sciences ◽

10.3390/ijms22031390 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1390

Author(s):

Julia Mester-Tonczar ◽

Patrick Einzinger ◽

Johannes Winkler ◽

Nina Kastner ◽

Andreas Spannbauer ◽

...

Keyword(s):

Myocardial Infarction ◽

Progenitor Cells ◽

Regulatory Networks ◽

Circular Rnas ◽

Cardiac Progenitor Cells ◽

Tissue Samples ◽

Healthy Myocardium ◽

Acute Mi

Circular RNAs (circRNAs) are crucial in gene regulatory networks and disease development, yet circRNA expression in myocardial infarction (MI) is poorly understood. Here, we harvested myocardium samples from domestic pigs 3 days after closed-chest reperfused MI or sham surgery. Cardiac circRNAs were identified by RNA-sequencing of rRNA-depleted RNA from infarcted and healthy myocardium tissue samples. Bioinformatics analysis was performed using the CIRIfull and KNIFE algorithms, and circRNAs identified with both algorithms were subjected to differential expression (DE) analysis and validation by qPCR. Circ-RCAN2 and circ-C12orf29 expressions were significantly downregulated in infarcted tissue compared to healthy pig heart. Sanger sequencing was performed to identify the backsplice junctions of circular transcripts. Finally, we compared the expressions of circ-C12orf29 and circ-RCAN2 between porcine cardiac progenitor cells (pCPCs) that were incubated in a hypoxia chamber for different time periods versus normoxic pCPCs. Circ-C12orf29 did not show significant DE in vitro, whereas circ-RCAN2 exhibited significant ischemia-time-dependent upregulation in hypoxic pCPCs. Overall, our results revealed novel cardiac circRNAs with DE patterns in pCPCs, and in infarcted and healthy myocardium. Circ-RCAN2 exhibited differential regulation by myocardial infarction in vivo and by hypoxia in vitro. These results will improve our understanding of circRNA regulation during acute MI.

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