Immune Cell Therapies to Improve Regeneration and Revascularization of Non-Healing Wounds

Groppa, Elena; Colliva, Andrea; Vuerich, Roman; Kocijan, Tea; Zacchigna, Serena

doi:10.3390/ijms21155235

Cited by 8 publications

(13 citation statements)

References 187 publications

(251 reference statements)

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“…Recently, lymphocytes have been highlighted as important cells that regulate wound healing responses. 6 – 8 We demonstrated a role for lymphocytes, specifically CD4 + lymphocytes, in regulation of dermal fibrosis in the severe combined immune deficient (SCID) mouse model. 9 Of the CD4 + subtypes, two immunoregulatory subsets stand out as producers of IL-10, CD4 + Foxp3 + regulatory T cells (Treg) which also produce transforming growth factor (TGF)-β and CD4 + Foxp3 - CD49b + Lag3 + type 1 regulatory T cells (Tr1) which additionally produce TGF-β, IFN-γ, and low levels of IL-4.…”

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confidence: 99%

Interleukin-10 Producing T Lymphocytes Attenuate Dermal Scarring

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Wang

et al. 2021

Annals of Surgery

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Objective: Demonstrate the impact of IL-10 producing T lymphocytes on mediating dermal scarring. Summary Background Data: We demonstrated that CD4 + cells are essential to improving postinjury wound healing and preventing fibrosis. CD4 + subsets secrete differential cytokine and growth factor profiles, though their role in fibrosis is not known. IL-10, a key anti-inflammatory cytokine shown to promote regenerative wound healing, is secreted by some CD4 + subsets. We, therefore, hypothesize that IL-10 producing CD4 + T lymphocyte subsets selectively attenuate dermal wound fibrosis. Methods: IL-10 -/- and wild-type murine splenocytes were enriched for CD4 + lymphocytes and adoptively transferred into severe combined immunodeficient (SCID) mice that received full-thickness wounds which were analyzed at days 7 and 28 for inflammation and collagen content. We then sorted CD4 + CD44 int/low FoxP3 - CD62L + T cells (Tnaive) or CD4 + CD44 Hi FoxP3 - type 1 regulatory (Tr1) T cell subsets from 10BiT murine splenocytes, activated them, and transferred them into wounds. In vitro , dermal fibroblasts were cocultured with Tnaive or Tr1 and the effect on extracellular matrix (ECM) regulation was analyzed. Results: The anti-inflammatory and antifibrotic effects of CD4 + cells on SCID wounds were lost with cells from IL-10 -/- mice. Adoptive transfer of Tr1 into SCID mice resulted in accelerated wound closure at d7 with reduced fibrosis at d28, with Tr1 favoring hyaluronan production by fibroblasts, an ECM molecule implicated in IL-10-induced regenerative healing. Conclusions: IL-10 producing T-lymphocytes, specifically Tr1, regulate inflammatory cell cytokine expression to promote HA-rich ECM deposition and attenuate fibrosis. Promoting IL-10 producing lymphocytes in wounds may be a therapeutic target to promote regenerative wound healing.

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confidence: 99%

Interleukin-10 Producing T Lymphocytes Attenuate Dermal Scarring

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Wang

et al. 2021

Annals of Surgery

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“…First, 2.5 × 10 5 ECs were resuspended in HESFM and seeded for 30 min at 37 • C, 5% v/v CO 2 , Integra ® Dermal Regeneration Template without a silicone layer (Integra ® Life Science Corporation) or PELNAC ® Dermal Substitute (Eurosurgical), that had previously been cut into small pieces (6 mm × 5 mm) using a sterile scalpel. After cell seeding, the scaffolds were directly implanted on the quadriceps of immunodeficient NOD scid gamma (NSG) mice [14]. Surgical implantation of the scaffolds was performed on adult NSG (8 weeks old) mice under general anesthesia by ketamine/xylazine (100 mg/kg and 10 mg/kg body weight, i.p.).…”

Section: Subcutaneously Application Of Admecs and In Vivo Experimentsmentioning

confidence: 99%

“…Since the formation of granulation tissue and leukocyte recruitment is fundamental for the restitutio ad integrum of wounds [14], we wanted to investigate the ability of the different scaffolds to induce ADMEC expression of the chemokine and cytokine genes involved in the inflammatory process. The results shown in Figure 5A-D Moreover, the upregulation of soluble angiogenetic factors (VEGF-A, PlGF and ANGPT-1) was also confirmed in terms of protein secretion (Figure 4I-K).…”

Section: Dermal Substitutes Modulate the Pro-inflammatory Behavior Of Admecmentioning

confidence: 99%

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Differential Capability of Clinically Employed Dermal Regeneration Scaffolds to Support Vascularization for Tissue Bioengineering

et al. 2021

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The loss of skin integrity has always represented a major challenge for clinicians dealing with dermal defects, such as ulcers (diabetic, vascular and chronic), postoncologic resections (i.e., radical vulvectomy) or dermatologic disorders. The introduction in recent decades of acellular dermal matrices (ADMs) supporting the repair and restoration of skin functionality represented a significant step toward achieving clean wound repair before performing skin grafts. Hard-to-heal ulcers generally depend on local ischemia and nonadequate vascularization. In this context, one possible innovative approach could be the prevascularization of matrices with vessel-forming cells (inosculation). This paper presents a comparative analysis of the most widely used dermal templates, i.e., Integra® Bilayer Matrix Wound Dressing, PELNAC®, PriMatrix® Dermal Repair Scaffold, Endoform® Natural Dermal Template, and Myriad Matrix®, testing their ability to be colonized by human adult dermal microvascular endothelial cells (ADMECs) and to induce and support angiogenesis in vitro and in vivo. By in vitro studies, we demonstrated that Integra® and PELNAC® possess superior pro-adhesive and pro-angiogenetic properties. Animal models allowed us to demonstrate the ability of preseeded ADMECs on Integra® to promote the engraftment, integration and vascularization of ADMs at the site of application.

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“…Acute wounds in diabetic patients can adopt and portray the chronicity of the nonhealing wounds due to bottom-line complications like the duration of diabetes or vascular disease paired with peripheral neuropathies [1]. Wounds that do not heal naturally within three months are defined as chronic wounds, and often require treatment to heal.…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory Properties of Host Defence Peptides in Skin Wound Healing

et al. 2021

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Cutaneous wound healing is a vital biological process that aids skin regeneration upon injury. Wound healing failure results from persistent inflammatory conditions observed in diabetes, or autoimmune diseases like psoriasis. Chronic wounds are incurable due to factors like poor oxygenation, aberrant function of peripheral sensory nervature, inadequate nutrients and blood tissue supply. The most significant hallmark of chronic wounds is heavily aberrant immune skin function. The immune response in humans relies on a large network of signalling molecules and their interactions. Research studies have reported on the dual role of host defence peptides (HDPs), which are also often called antimicrobial peptides (AMPs). Their duality reflects their potential for acting as antibacterial peptides, and as immunodulators that assist in modulating several biological signalling pathways related to processes such as wound healing, autoimmune disease, and others. HDPs may differentially control gene regulation and alter the behaviour of epithelial and immune cells, resulting in modulation of immune responses. In this review, we shed light on the understanding and most recent advances related to molecular mechanisms and immune modulatory features of host defence peptides in human skin wound healing. Understanding their functional role in skin immunity may further inspire topical treatments for chronic wounds.

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Immune Cell Therapies to Improve Regeneration and Revascularization of Non-Healing Wounds

Cited by 8 publications

References 187 publications

Interleukin-10 Producing T Lymphocytes Attenuate Dermal Scarring

Interleukin-10 Producing T Lymphocytes Attenuate Dermal Scarring

Differential Capability of Clinically Employed Dermal Regeneration Scaffolds to Support Vascularization for Tissue Bioengineering

Immunomodulatory Properties of Host Defence Peptides in Skin Wound Healing

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