Direct transplantation of native pericytes from adipose tissue: A new perspective to stimulate healing in critical size bone defects

König, Matthias; Canepa, Daisy D.; Cadosch, Dieter; Casanova, Elisa A.; Heinzelmann, Michael; Rittirsch, Daniel; Plecko, Michael; Hemmi, Sonja; Simmen, Hans‐Peter; Cinelli, Paolo; Wanner, Guido A.

doi:10.1016/j.jcyt.2015.10.002

Cited by 34 publications

(22 citation statements)

References 44 publications

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“…While both purified pericytes and adventitial stromal cells yield MSCs in vitro , their respective contributions to long‐term conventional MSC cultures are unknown. However, description of gene expression in single cells has revealed that adventitial stromal cells are developmentally more primitive than pericytes , although we and other investigators have previously documented the strong regenerative potential of pericytes purified from AT . Therefore, if the therapeutic value of Lipogems is related to pericyte enrichment, those cells might exert their regenerative action more indirectly, via growth factor secretion, than as progenitor cells.…”

Section: Discussionmentioning

confidence: 83%

Higher Pericyte Content and Secretory Activity of Microfragmented Human Adipose Tissue Compared to Enzymatically Derived Stromal Vascular Fraction

Vezzani

Shaw

Lesme

et al. 2018

Stem Cells Translational Medicine

115

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Autologous adipose tissue is used for tissue repletion and/or regeneration as an intact lipoaspirate or as enzymatically derived stromal vascular fraction (SVF), which may be first cultured into mesenchymal stem cells (MSCs). Alternatively, transplant of autologous adipose tissue mechanically fragmented into submillimeter clusters has recently showed remarkable efficacy in diverse therapeutic indications. To document the biologic basis of the regenerative potential of microfragmented adipose tissue, we first analyzed the distribution of perivascular presumptive MSCs in adipose tissue processed with the Lipogems technology, observing a significant enrichment in pericytes, at the expense of adventitial cells, as compared to isogenic enzymatically processed lipoaspirates. The importance of MSCs as trophic and immunomodulatory cells, due to the secretion of specific factors, has been described. Therefore, we investigated protein secretion by cultured adipose tissue clusters or enzymatically derived SVF using secretome arrays. In culture, microfragmented adipose tissue releases many more growth factors and cytokines involved in tissue repair and regeneration, noticeably via angiogenesis, compared to isogenic SVF. Therefore, we suggest that the efficient tissue repair/regeneration observed after transplantation of microfragmented adipose tissue is due to the secretory ability of the intact perivascular niche. Stem Cells Translational Medicine 2018;7:876–886

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Section: Discussionmentioning

confidence: 83%

Higher Pericyte Content and Secretory Activity of Microfragmented Human Adipose Tissue Compared to Enzymatically Derived Stromal Vascular Fraction

Vezzani

Shaw

Lesme

et al. 2018

Stem Cells Translational Medicine

115

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show abstract

“…Pericytes (CD146 + NG2 + CD45 − ) isolated from mouse fat tissue display osteogenic potential in vitro which is mirrored in vivo by contributing to the regeneration of mouse bone injury when applied in a seeded scaffold [26]. Similarly, human adipose derived pericytes (CD146 + CD34 − CD45 − CD31 − ) enhance bone healing and encourage bone-union in mouse bone fractures with equal efficacy to BM-MSCs [90].…”

Section: Pericytes As a Therapeutic Agentmentioning

confidence: 99%

“…We now understand that pericytes not only express MSC markers but also possess MSC-like properties, and display the ability to differentiate in vitro into an array of mesenchymal cell types. These include adipocytes [25], osteoblasts, chondrocytes [26], phagocytes and granulocytes [2]. The potential for pericytes to differentiate into beneficial cell types during the proliferative and regenerative stages of wound healing is an exciting prospect, and in the context of wound healing a cell type with the potential to positively contribute to direct regeneration of lost tissue represents a possible target for therapeutics or a source for the development of a cell-based therapy.…”

Section: An Introduction To Pericytesmentioning

confidence: 99%

The Importance of Pericytes in Healing: Wounds and other Pathologies

Thomas

Cowin

Mills

2017

IJMS

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Much of current research investigates the beneficial properties of mesenchymal stem cells (MSCs) as a treatment for wounds and other forms of injury. In this review, we bring attention to and discuss the role of the pericyte, a cell type which shares much of the differentiation potential and regenerative properties of the MSC as well as specific roles in the regulation of angiogenesis, inflammation and fibrosis. Pericytes have been identified as dysfunctional or depleted in many disease states, and observing the outcomes of pericyte perturbation in models of disease and wound healing informs our understanding of overall pericyte function and identifies these cells as an important target in the development of therapies to encourage healing.

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“…CD146+/CD45−/CD34−/CD56− human cells expressed a variety of pericyte markers (NG2, PDGFRβ, and αSMA) and gave rise in culture to cells with MSCs features, including expression of typical MSC markers, migration in a culture model of chemotaxis, classical trilineage differentiation in vitro and myogenic and osteogenic differentiation in vivo in mice. Alternative strategies to isolate pericytes have been reported including simplified versions of the antibody panel used by Crisan et al in human and mice or the inclusion of additional antibodies to isolate pericytes from human skeletal muscle. As such, cells have been isolated from human heart (CD146+/CD34−/CD45−/CD56−/CD117−) , umbilical cord (CD146+/CD45−/CD34−/CD56−), skeletal muscle (alkaline phosphatase (ALP)+/CD56−) and endometrium (CD146+/PDGFRβ+) , while trace amounts of cells (0.04%) natively expressing MSC markers (CD105+/CD73+/CD90+/CD34‐/CD45−) have also been detected in human adipose .…”

Section: Prospective Isolation and Characterization Of Pericytesmentioning

confidence: 99%

Pericytes and their potential in regenerative medicine across species

Esteves

Donadeu

2017

Cytometry Pt A

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The discovery that pericytes are in vivo counterparts of Mesenchymal Stem/Stromal Cells (MSCs) has placed these perivascular cells in the research spotlight, bringing up hope for a well-characterized cell source for clinical applications, alternative to poorly defined, heterogeneous MSCs preparations currently in use. Native pericytes express typical MSC markers and, after isolation by fluorescence-activated cell sorting, display an MSC phenotype in culture. These features have been demonstrated in different species, including humans and horses, the main targets of regenerative treatments. Significant clinical potential of pericytes has been shown by transplantation of human cells into rodent models of tissue injury, and it is hoped that future studies will demonstrate clinical potential in veterinary species. Here, we provide an overview of the current knowledge on pericytes across different species including humans, companion and large animal models, in relation to their identification in different body tissues, methodology for prospective isolation, characterization, and potential for tissue regeneration. © 2017 International Society for Advancement of Cytometry.

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Direct transplantation of native pericytes from adipose tissue: A new perspective to stimulate healing in critical size bone defects

Cited by 34 publications

References 44 publications

Higher Pericyte Content and Secretory Activity of Microfragmented Human Adipose Tissue Compared to Enzymatically Derived Stromal Vascular Fraction

Higher Pericyte Content and Secretory Activity of Microfragmented Human Adipose Tissue Compared to Enzymatically Derived Stromal Vascular Fraction

The Importance of Pericytes in Healing: Wounds and other Pathologies

Pericytes and their potential in regenerative medicine across species

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