Tissue origin of cytotoxic natural killer cells dictates their differential roles in mouse digit tip regeneration and progenitor cell survival

Dastagir, Nadjib; Beal, Zachery; Godwin, James

doi:10.1016/j.stemcr.2022.01.006

Cited by 7 publications

(6 citation statements)

References 40 publications

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“…Activated cytotoxic NK cells exert killing by delivering lytic granules or secreting death-inducing cytokines [ 168 ]. Dastagir et al [ 169 ] have found that NK cells are recruited to regenerating digit tips, and have observed NK cytotoxicity against osteoclast and osteoblast progenitors. The authors have concluded that stem cell proliferation and differentiation are mediated through multiple routes by distinct NK cell subsets.…”

Section: Immune Microenvironment In Tissue Regenerationmentioning

confidence: 99%

The role of the immune microenvironment in bone, cartilage, and soft tissue regeneration: from mechanism to therapeutic opportunity

Xiong

Lin

et al. 2022

Military Med Res

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Bone, cartilage, and soft tissue regeneration is a complex spatiotemporal process recruiting a variety of cell types, whose activity and interplay must be precisely mediated for effective healing post-injury. Although extensive strides have been made in the understanding of the immune microenvironment processes governing bone, cartilage, and soft tissue regeneration, effective clinical translation of these mechanisms remains a challenge. Regulation of the immune microenvironment is increasingly becoming a favorable target for bone, cartilage, and soft tissue regeneration; therefore, an in-depth understanding of the communication between immune cells and functional tissue cells would be valuable. Herein, we review the regulatory role of the immune microenvironment in the promotion and maintenance of stem cell states in the context of bone, cartilage, and soft tissue repair and regeneration. We discuss the roles of various immune cell subsets in bone, cartilage, and soft tissue repair and regeneration processes and introduce novel strategies, for example, biomaterial-targeting of immune cell activity, aimed at regulating healing. Understanding the mechanisms of the crosstalk between the immune microenvironment and regeneration pathways may shed light on new therapeutic opportunities for enhancing bone, cartilage, and soft tissue regeneration through regulation of the immune microenvironment.

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Section: Immune Microenvironment In Tissue Regenerationmentioning

confidence: 99%

The role of the immune microenvironment in bone, cartilage, and soft tissue regeneration: from mechanism to therapeutic opportunity

Xiong

Lin

et al. 2022

Military Med Res

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show abstract

“…Mice that had their macrophages depleted exhibited abnormal or failed digit tip regeneration due to an inhibition of bone histolysis and wound closure ( Simkin et al, 2017 ). Similarly, natural killer cells are also necessary for digit tip regeneration, as ablation leads to delayed bone histolysis and delayed bone formation ( Dastagir et al, 2022 ). There are still major areas of uncertainty pertaining to the inflammatory response in proximal digit amputations.…”

Section: Discussionmentioning

confidence: 99%

“…All these tissues are lost to varying degrees with digit tip amputation and are subsequently regenerated, which occurs in the following broad steps: inflammation, histolysis, wound closure, blastema formation, and differentiation ( Simkin et al, 2015a ). Following digit tip amputation, a blood clot forms at the wound site and inflammation occurs as immune cells, including neutrophils, natural killer cells, and macrophages, infiltrate the tissues ( Simkin et al, 2017 ; Dastagir et al, 2022 ). At the later stages of the immune response, osteoclasts degrade the distal stump bone until the epidermis closes from both dorsal and ventral sides to form the wound epidermis, a structure that is a signaling source for regeneration ( Lee et al, 2013 ; Takeo et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Toeing the line between regeneration and fibrosis

Jou

Lehoczky

2023

Front. Cell Dev. Biol.

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Understanding the remarkable capacity of vertebrates to naturally regenerate injured body parts has great importance for potential translation into human therapeutic applications. As compared to other vertebrates, mammals have low regenerative capacity for composite tissues like the limb. However, some primates and rodents can regenerate the distal tips of their digits following amputation, indicating that at least very distal mammalian limb tissues are competent for innate regeneration. It follows that successful digit tip regenerative outcome is highly dependent on the location of the amputation; those proximal to the position of the nail organ do not regenerate and result in fibrosis. This distal regeneration versus proximal fibrosis duality of the mouse digit tip serves as a powerful model to investigate the driving factors in determining each process. In this review, we present the current understanding of distal digit tip regeneration in the context of cellular heterogeneity and the potential for different cell types to function as progenitor cells, in pro-regenerative signaling, or in moderating fibrosis. We then go on to discuss these themes in the context of what is known about proximal digit fibrosis, towards generating hypotheses for these distinct healing processes in the distal and proximal mouse digit.

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“…Early work suggested that NK cell activity was suppressed in fracture patients; whereas recent studies indicate an important role for NK cells in MSC recruitment to the fracture site through neutrophil activating peptide 2 secretion, and in regulation of osteoclastogenesis ( 42 – 44 ). Different classes of NK cells regulate progenitor cell survival during digit tip regeneration that may be comparable to events during fracture healing ( 45 ). NK cells also show interdependency with MSC, where MSC secretion of IL-10, transforming growth factor beta (TGF-β), and prostaglandin E2 (PGE2), has been linked to suppression of NK cells ( 46 – 48 ).…”

Section: Hematoma Formation and Inflammatory Phasementioning

confidence: 99%

Temporal dynamics of immune-stromal cell interactions in fracture healing

Capobianco,

Hankenson,

Knights

2024

Front. Immunol.

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Bone fracture repair is a complex, multi-step process that involves communication between immune and stromal cells to coordinate the repair and regeneration of damaged tissue. In the US, 10% of all bone fractures do not heal properly without intervention, resulting in non-union. Complications from non-union fractures are physically and financially debilitating. We now appreciate the important role that immune cells play in tissue repair, and the necessity of the inflammatory response in initiating healing after skeletal trauma. The temporal dynamics of immune and stromal cell populations have been well characterized across the stages of fracture healing. Recent studies have begun to untangle the intricate mechanisms driving the immune response during normal or atypical, delayed healing. Various in vivo models of fracture healing, including genetic knockouts, as well as in vitro models of the fracture callus, have been implemented to enable experimental manipulation of the heterogeneous cellular environment. The goals of this review are to (1): summarize our current understanding of immune cell involvement in fracture healing (2); describe state-of-the art approaches to study inflammatory cells in fracture healing, including computational and in vitro models; and (3) identify gaps in our knowledge concerning immune-stromal crosstalk during bone healing.

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Tissue origin of cytotoxic natural killer cells dictates their differential roles in mouse digit tip regeneration and progenitor cell survival

Cited by 7 publications

References 40 publications

The role of the immune microenvironment in bone, cartilage, and soft tissue regeneration: from mechanism to therapeutic opportunity

The role of the immune microenvironment in bone, cartilage, and soft tissue regeneration: from mechanism to therapeutic opportunity

Toeing the line between regeneration and fibrosis

Temporal dynamics of immune-stromal cell interactions in fracture healing

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