Natural killer cell crosstalk with allogeneic human cardiac-derived stem/progenitor cells controls persistence

Boukouaci, Wahid; Lauden, Laura; Siewiera, Johan; Dam, Noémie; Hocine, Hocine R.; Khaznadar, Zena; Tamouza, Ryad; Borlado, Luis R.; Charron, Dominique; Jabrane‐Ferrat, Nabila; Al-Daccak, Reem

doi:10.1093/cvr/cvu208

Cited by 40 publications

(42 citation statements)

References 33 publications

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“…In the absence of anti-HLA-I or –HLA-II antibodies and in accordance with our previous report demonstrating that inflammatory-environment-inured hCPC are less susceptible to allogeneic NK cell killing10, up to 35–40% of allogeneic NK cells expressed CD137 and degranulated when co-cultured with hCPC, while only 20% of those interacting with IFNγ-hCPC (Fig. 3a upper panel, and Supplementary Figs 3 and 4).…”

Section: Resultssupporting

confidence: 92%

“…In addition to off-the-shelf availability, allogeneic hCPC-based therapy has become a prominent strategy for cardiac repair because of their favorable allogeneic cellular immune consequences that have been linked, in part or as whole, to their beneficial effects7810. Herein, by using an hCPC-tailored flow cytometry-based assay, we demonstrate that allogeneic hCPC are prone to DSA-HLA-I-induced injury but seem rather invulnerable to DSA-HLA-II.…”

Section: Discussionmentioning

confidence: 92%

“…This applies to mesenchymal stem cells, cardiosphere-derived cells (CDC), and cardiac-derived stem/progenitor cells (CPC). Moreover, our previous findings also highlight the allogenecity of human CPC as part of the dynamic mechanisms that are critical for the maintenance of sustainable cardiac repair810. All together, these findings prompted the initiation of two clinical trials using allogeneic cardiac stem/progenitor cells: the ALLSTAR (http://clinicaltrials.gov/show/NCT01458405) and the CAREMI (https://clinicaltrials.gov/ct2/show/NCT02439398) in patients with acute myocardial infarction (MI).…”

mentioning

confidence: 78%

“…Currently, a large body of in vitro and in vivo research indicates that the allogeneic stem/progenitor cells are safe since they activate modulatory rather than deleterious cellular immune reactions5678910. This applies to mesenchymal stem cells, cardiosphere-derived cells (CDC), and cardiac-derived stem/progenitor cells (CPC).…”

mentioning

confidence: 99%

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Minimizing the risk of allo-sensitization to optimize the benefit of allogeneic cardiac-derived stem/progenitor cells

Hocine¹,

Costa²,

Dam³

et al. 2017

Sci Rep

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Allogeneic human cardiac-derived stem/progenitor cells (hCPC) are currently under clinical investigation for cardiac repair. While cellular immune response against allogeneic hCPC could be part of their beneficial-paracrine effects, their humoral immune response remains largely unexplored. Donor-specific HLA antibodies (DSA-HLA-I/DSA-HLA-II), primary elements of antibody-mediated allograft injury, might present an unidentified risk to allogeneic hCPC therapy. Here we established that the binding strength of anti-HLA monoclonal antibodies delineates hCPC proneness to antibody-mediated injury. In vitro modeling of clinical setting demonstrated that specific DSA-HLA-I of high/intermediate binding strength are harmful for hCPC whereas DSA-HLA-II are benign. Furthermore, the Luminex-based solid-phase assays are suitable to predict the DSA-HLA risk to therapeutic hCPC. Our data indicate that screening patient sera for the presence of HLA antibodies is important to provide an immune-educated choice of allogeneic therapeutic cells, minimize the risk of precipitous elimination and promote the allogeneic reparative effects.

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Section: Resultssupporting

confidence: 92%

Section: Discussionmentioning

confidence: 92%

mentioning

confidence: 78%

mentioning

confidence: 99%

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Minimizing the risk of allo-sensitization to optimize the benefit of allogeneic cardiac-derived stem/progenitor cells

Hocine¹,

Costa²,

Dam³

et al. 2017

Sci Rep

Self Cite

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“…This tolerogenic phenomenon was shown to be the result of a cell contact-dependent expansion and activation of regulatory T cells through the PD1–PDL1 pathway, which was amplified under inflammatory conditions. In addition, hypoxic hCSCs are also able to downregulate NK cell–mediated cytotoxicity and to polarize NK cells toward secretion of anti-inflammatory cytokines IL10 and IL13 rather than inflammatory IFNγ and TNFα [19]. We therefore proposed the benefits of using allogeneic cells maintained through hypoxic conditions with the potential paracrine effect on endogenous cardiogenesis [9].…”

Section: Cardiac Stem Cellsmentioning

confidence: 99%

Immune responses to bioengineered organs

Ochando

Charron

Baptista

et al. 2017

Current Opinion in Organ Transplantation

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Purpose of reviewOrgan donation in the United States registered 9079 deceased organ donors in 2015. This high percentage of donations allowed organ transplantation in 29 851 recipients. Despite increasing numbers of transplants performed in comparison with previous years, the numbers of patients that are in need for a transplant increase every year at a higher rate. This reveals that the discrepancy between the demand and availability of organs remains fundamental problem in organ transplantation.Recent findingsDevelopment of bioengineered organs represents a promising approach to increase the pool of organs for transplantation. The technology involves obtaining complex three-dimensional scaffolds that support cellular activity and functional remodeling though tissue recellularization protocols using progenitor cells. This innovative approach integrates cross-thematic approaches from specific areas of transplant immunology, tissue engineering and stem cell biology, to potentially manufacture an unlimited source of donor organs for transplantation.SummaryAlthough bioengineered organs are thought to escape immune recognition, the potential immune reactivity toward each of its components has not been studied in detail. Here, we summarize the host immune response toward different progenitor cells and discuss the potential implications of using nonself biological scaffolds to develop bioengineered organs.

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Adult stem cell niches for tissue homeostasis

Mannino

Russo

Maugeri

et al. 2021

Journal Cellular Physiology

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Adult stem cells are fundamental to maintain tissue homeostasis, growth, and regeneration. They reside in specialized environments called niches. Following activating signals, they proliferate and differentiate into functional cells that are able to preserve tissue physiology, either to guarantee normal turnover or to counteract tissue damage caused by injury or disease. Multiple interactions occur within the niche between stem cell-intrinsic factors, supporting cells, the extracellular matrix, and signaling pathways. Altogether, these interactions govern cell fate, preserving the stem cell pool, and regulating stem cell proliferation and differentiation. Based on their response to body needs, tissues can be largely classified into three main categories: tissues that even in normal conditions are characterized by an impressive turnover to replace rapidly exhausting cells (blood, epidermis, or intestinal epithelium); tissues that normally require only a basal cell replacement, though able to efficiently respond to increased tissue needs, injury, or disease (skeletal muscle); tissues that are equipped with less powerful stem cell niches, whose repairing ability is not able to overcome severe damage (heart or nervous tissue). The purpose of this review is to describe the main characteristics of stem cell niches in these different tissues, highlighting the various components influencing stem cell activity. Although much has been done, more work is needed to further increase our knowledge of niche interactions. This would be important not only to shed light on this fundamental chapter of human physiology but also to help the development of cell-based strategies for clinical therapeutic applications, especially when other approaches fail.

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Natural killer cell crosstalk with allogeneic human cardiac-derived stem/progenitor cells controls persistence

Abstract: Collectively, our data suggest that allogeneic hCPC/innate NK cells crosstalk within injured inflamed myocardium would permit their retention and might contribute to attenuating inflammation and to preventing adverse cardiac remodelling.

Cited by 40 publications

References 33 publications

Minimizing the risk of allo-sensitization to optimize the benefit of allogeneic cardiac-derived stem/progenitor cells

Minimizing the risk of allo-sensitization to optimize the benefit of allogeneic cardiac-derived stem/progenitor cells

Immune responses to bioengineered organs

Adult stem cell niches for tissue homeostasis

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