No Identical “Mesenchymal Stem Cells” at Different Times and Sites: Human Committed Progenitors of Distinct Origin and Differentiation Potential Are Incorporated as Adventitial Cells in Microvessels

Sacchetti, Benedetto; Funari, Alessia; Remoli, Cristina; Giannicola, Giuseppe; Kögler, Gesine; Liedtke, Stefanie; Cossu, Giulio; Serafini, Marta; Sampaolesi, Maurilio; Tagliafico, Enrico; Tenedini, Elena; Saggio, Isabella; Robey, Pamela Gehron; Riminucci, Mara; Bianco, Paolo

doi:10.1016/j.stemcr.2016.05.011

Cited by 372 publications

(404 citation statements)

References 42 publications

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“…In vitro, CB-BFs display osteogenic and chondrogenic differentiation potential , whereas they have a reduced or virtually absent capacity to generate adipocyte-like cells (Kern et al, 2006;Goodwin et al, 2001;Zhang et al, 2011;Bieback et al, 2008;Karagianni et al, 2013). When transplanted in vivo with osteoconductive ceramic scaffolds, CB-BFs are able to form histology-proven bone (Zhang et al, 2011;Liedtke et al, 2016;Sacchetti et al, 2016). Interestingly, we have also demonstrated that CB-BFs consistently form cartilage in open heterotopic transplants, a property that is usually not observed in BMSCs.…”

Section: Introductionsupporting

confidence: 53%

“…The cartilaginous tissue was formed in the absence of any ex vivo induction, thus demonstrating the inherent capacity of CB-BFs to undergo chondrogenesis even in the absence of specific inducing agents . However, in none of the previous studies was CB-BF differentiation associated with the establishment of a hematopoietic microenvironment (Zhang et al, 2011;Sacchetti et al, 2016). The results presented here provide further elucidation of the biology of CB-BFs, demonstrating that CBBFs were able to generate complete pellet-derived ossicles in vivo in which a functional HSC niche was created.…”

Section: Discussionmentioning

confidence: 63%

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Human umbilical cord blood-borne fibroblasts contain marrow niche precursors that form a bone/marrow organoid in vivo

et al. 2017

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Human umbilical cord blood (CB) has attracted much attention as a reservoir for functional hematopoietic stem and progenitor cells, and, recently, as a source of blood-borne fibroblasts (CB-BFs). Previously, we demonstrated that bone marrow stromal cell (BMSC) and CB-BF pellet cultures make cartilage in vitro. Furthermore, upon in vivo transplantation, BMSC pellets remodelled into miniature bone/marrow organoids. Using this in vivo model, we asked whether CB-BF populations that express characteristics of the hematopoietic stem cell (HSC) niche contain precursors that reform the niche. CB ossicles were regularly observed upon transplantation. Compared with BM ossicles, CB ossicles showed a predominance of red marrow over yellow marrow, as demonstrated by histomorphological analyses and the number of hematopoietic cells isolated within ossicles. Marrow cavities from CB and BM ossicles included donor-derived CD146-expressing osteoprogenitors and host-derived mature hematopoietic cells, clonogenic lineage-committed progenitors and HSCs. Furthermore, human CD34+ cells transplanted into ossicle-bearing mice engrafted and maintained human HSCs in the niche. Our data indicate that CBBFs are able to recapitulate the conditions by which the bone marrow microenvironment is formed and establish complete HSC niches, which are functionally supportive of hematopoietic tissue.

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Section: Introductionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 63%

Human umbilical cord blood-borne fibroblasts contain marrow niche precursors that form a bone/marrow organoid in vivo

et al. 2017

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“…Mesenchymal "stem" cells (MSCs) have been isolated from virtually all tissues and organs, however, the lack of specific markers has made their characterisation challenging, particularly in light of a recent report showing that mesenchymal stromal cells from different tissues have different transcriptome profiles and differentiation potentials (Sacchetti et al, 2016). Given the advanced state of analysis interstitial cells in muscle, it would be important to establish their lineage relationships and myogenic potential, and define more clearly general features of MSCs.…”

Section: Cellular Regulators Of Muscle Repair and Their Regenerativementioning

confidence: 99%

Regulation and phylogeny of skeletal muscle regeneration

Baghdadi

Tajbakhsh

2018

Developmental Biology

158

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One of the most fascinating questions in regenerative biology is why some animals can regenerate injured structures while others cannot. Skeletal muscle has a remarkable capacity to regenerate even after repeated traumas, yet limited information is available on muscle repair mechanisms and how they have evolved. For decades, the main focus in the study of muscle regeneration was on muscle stem cells, however, their interaction with their progeny and stromal cells is only starting to emerge, and this is crucial for successful repair and reestablishment of homeostasis after injury. In addition, numerous murine injury models are used to investigate the regeneration process, and some can lead to discrepancies in observed phenotypes. This review addresses these issues and provides an overview of the some of the main regulatory cellular and molecular players involved in skeletal muscle repair.Key words: skeletal muscle, regeneration, stem cells, evolution, quiescence, injury IntroductionThe ability to regenerate tissues and structures is a prevalent feature of metazoans although there is significant variability among species ranging from limited regeneration of a tissue (birds and mammals) to regeneration involving the entire organism (cnidarians, planarians, hydra). The intriguing evolutionary loss of regenerative capacity in more complex organisms highlights the importance of identifying the underlying mechanisms responsible for these diverse regenerative strategies. One of the most studied tissues that contributes to new appendage formation is skeletal muscle, thereby making it a major focus of regeneration studies during evolution. The emergence of new lineage-tracing tools in different animal models has permitted the identification of specific progenitor cell populations and their contribution to tissue repair.Skeletal muscles allow voluntary movement and they play a key role in regulating metabolism and homeostasis in the organism. In mice and humans this tissue represents about 30-40% of the total body mass. This tissue provides an excellent tractable model to study regenerative myogenesis and the relative roles of stem and stromal cells following a single, or repeated rounds of injury. Although muscle regeneration relies mainly on its resident muscle stem (satellite) cells (MuSCs) to effect muscle repair, interactions with neighbouring stromal cells, by direct contact or via the release of soluble factors, is essential to restore proper 3 function. Each step of the myogenic process is regulated by specific regulatory factors including extrinsic cues, yet the nature and source of these signals remain unclear. This review will address these issues and discuss the different experimental models used to investigate the regenerative process. Prenatal and postnatal skeletal muscle developmentIn amniotes, skeletal muscles in the limbs and trunk arise from somites through a series of successive waves that include embryonic and foetal phases of myoblast production (Biressi et al., 2007;Comai and Tajbakhsh, 201...

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“…BM-MSCs are endowed with the ability to differentiate in four canonical lineages, osteoblasts, chondroblasts, adipoblasts and reticular stromal cells supporting HSCs, underlying their regenerative activity. MSCs were first discovered in BM, (other) tissue-specific MSCs have been recently recognized and studied [30,27,24,2]. In this manuscript, we utilize primary peri-cryptic colonic SMA + MSCs endowed with all BM MSCs functions but adipogenesis [30] to explore the role of miR-204&211 in their differentiation.…”

Section: Discussionmentioning

confidence: 99%

Effect of miR-204&211 and RUNX2 control on the fate of human mesenchymal stromal cells

et al. 2017

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--MiR-204 and 211 enforced expression in murine mesenchymal stromal cells (MSCs) has been shown to induce adipogenesis and impair osteogenesis, through RUNX2 down-modulation. This mechanism has been suggested to play a role in osteoporosis associated with obesity. However, two further fundamental MSC functions, chondrogenesis and hematopoietic supporting activity, have not yet been explored. To this end, we transduced, by a lenti-viral vector, miR-204 and 211 in a model primary human MSC line, opportunely chosen among our MSC collection for displaying all properties of canonical bone marrow MSCs, except adipogenesis. Enforced expression of miR-204&211 in these cells, rescued adipogenesis, and inhibited osteogenesis, as previously reported in murine MSCs, but, surprisingly, also damaged cartilage formation and hematopoietic supporting activity, which were never explored before. RUNX2 has been previously indicated as the target of miR-204&211, whose down modulation is responsible for the switch from osteogenesis to adipogenesis. However, the additional disruption of chondrogenesis and hematopoietic supporting activity, which we report here, might depend on diverse miR-204&211 targets. To investigate this hypothesis, permanent RUNX2 knock-down was performed. Sh-RUNX2 fully reproduced the phenotypes induced by miR-204&211, confirming that RUNX2 down modulation is the major event leading to the reported functional modification on our MSCs. It seems thus apparent that RUNX2, a recognized master gene for osteogenesis, might rule all four MSC commitment and differentiation processes. Hence, the formerly reported role of miR204&211 and RUNX2 in osteoporosis and obesity, coupled with our novel observation showing inhibition of cartilage differentiation and hematopoietic support, strikingly resemble the clinical traits of metabolic syndrome, where osteoarthritis, osteoporosis, anaemia and obesity occur together. Our observations, corroborating and extending previous observations, suggest that miR-204&211-RUNX2 axis in human MSCs is possibly involved in the pathogenesis of this rapidly growing disease in industrialized countries, for possible therapeutic intervention to regenerate former homeostasis.

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No Identical “Mesenchymal Stem Cells” at Different Times and Sites: Human Committed Progenitors of Distinct Origin and Differentiation Potential Are Incorporated as Adventitial Cells in Microvessels

Cited by 372 publications

References 42 publications

Human umbilical cord blood-borne fibroblasts contain marrow niche precursors that form a bone/marrow organoid in vivo

Human umbilical cord blood-borne fibroblasts contain marrow niche precursors that form a bone/marrow organoid in vivo

Regulation and phylogeny of skeletal muscle regeneration

Effect of miR-204&211 and RUNX2 control on the fate of human mesenchymal stromal cells

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