Painting factor H onto mesenchymal stem cells protects the cells from complement- and neutrophil-mediated damage

Li, Yan; Qiu, Wen; Zhang, Lingjun; Fung, John J.; Lin, Feng

doi:10.1016/j.imbio.2016.06.020

Cited by 7 publications

(17 citation statements)

References 38 publications

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“…53 Similar conjugation schemes have been adopted for coating factor H proteins onto the surface of mesenchymal stem cells, thereby protecting them from complement attack. 54 Mimicking how bacteria evade the human immune system by hijacking regulatory proteins, Wu et al developed an alternative method to tether factor H-binding peptides covalently onto polystyrene surfaces, and when incubated in serum, factor H proteins became bound to this functionalized surface and significantly inhibited complement activation. 55,56 Based on the aforementioned studies, there is strong evidence supporting that factor H coatings are an excellent biomimetic strategy to reduce complement activation.…”

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confidence: 99%

Stealth Immune Properties of Graphene Oxide Enabled by Surface-Bound Complement Factor H

et al. 2016

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With mounting evidence that nanomaterials can trigger adverse innate immune responses such as complement activation, there is increasing attention to the development of strategies that mask the complement-activating properties of nanomaterials. The current gold standard to reduce complement activation of nanomaterials is the covalent attachment of polymer coatings on nanomaterial surfaces, even though this strategy provides only moderate protection against complement activation. Akin to protein coronas that form on nanomaterial surfaces in physiological fluids, noncovalent strategies based on protein adsorption would offer a simplified, biomimetic approach to mitigate complement activation. Herein, we demonstrate that precoating graphene-based nanomaterials with purified, natural proteins enables regulatory control of nanomaterial-triggered complement activation. When the graphene-based nanomaterials were coated with complement factor H, nearly complete protection (>90% reduction) against complement activation (a "stealth effect") was achieved. By contrast, coating the nanomaterials with a passivating layer of bovine or human serum albumins achieved moderate protection (∼40% reduction), whereas immunoglobulin G amplified complement activation by several-fold. Taken together, our results demonstrate that surface-bound factor H, as well as serum albumins, can prevent graphene oxide-triggered complement activation, thereby offering a facile approach to inhibit complement activation completely down to naturally occurring levels.

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confidence: 99%

Stealth Immune Properties of Graphene Oxide Enabled by Surface-Bound Complement Factor H

et al. 2016

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“…The important question of whether the anti-donor antibody response to allogeneic MSCs has the potential to cause immunological 'rejection' of the implanted MSCs (or of subsequent doses of allogeneic MSCs) remains unclear. Theoretically, this could occur directly through activation of the classical complement activation pathway, through complement-mediated activation of innate immune cells such as neutrophils, macrophages and natural killer cells or through concomitant anti-donor CD4 þ and CD8 þ T-cell responses 17,[37][38][39] . Our observation of equivalent efficacy of autologous and allogeneic MSCs in the hindlimb ischemic model suggests that anti-donor immunogenicity did not compromise the beneficial effect of a single injection of intramuscular B6 MSC in db/db recipients.…”

Section: Discussionmentioning

confidence: 99%

Allogeneic Mesenchymal Stromal Cells (MSCs) are of Comparable Efficacy to Syngeneic MSCs for Therapeutic Revascularization in C57BKSdb/db Mice Despite the Induction of Alloantibody

et al. 2018

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Intramuscular administration of mesenchymal stromal cells (MSCs) represents a therapeutic option for diabetic critical limb ischemia. Autologous or allogeneic approaches may be used but disease-induced cell dysfunction may limit therapeutic efficacy in the former. Our aim was to compare the efficacy of allogeneic and autologous MSC transplantation in a model of hindlimb ischemia in diabetes mellitus and to determine whether allogeneic transplantation would result in the activation of an immune response. MSCs were isolated from C57BL/6 (B6) and diabetic obese C57BKS mice. Phosphate-buffered saline (control group), and MSCs (1 × 10) from B6 (allogeneic group) or C57BKS (syngeneic group) were administered intramuscularly into the ischemic thigh of C57BKS mice following the induction of hindlimb ischemia. MSCs derived from both mouse strains secrete several angiogenic factors, suggesting that the potential therapeutic effect is due to paracrine signaling. Administration of allogeneic MSCs significantly improved blood perfusion as compared with the control group on week 2 and 3, post-operatively. In comparison with the control group, syngeneic MSCs significantly improved blood perfusion at week 2 only. There was no statistical difference in blood perfusion between allogeneic and syngeneic MSC groups at any stages. There was no statistical difference in ambulatory and necrosis score among the three groups. Amputation of toes was only observed in the control group (one out of seven animals). Alloantibody was detected in three out of the eight mice that received allogeneic MSCs but was not observed in the other groups. In summary, we demonstrated comparable efficacy after transplantation of autologous and allogeneic MSCs in a diabetic animal model despite generation of an immune response.

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“…For example, Lin et al . have reported that release of C5a following complement fixation by MSC results in activation of neutrophils and cell damage via the resulting oxidative burst . Furthermore, the complement cleavage product iC3b may serve as an activating ligand to enhance NK cell‐mediated lysis of MSC in vivo …”

Section: Discussionmentioning

confidence: 99%

Anti‐donor antibody induction following intramuscular injections of allogeneic mesenchymal stromal cells

et al. 2018

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Allogeneic mesenchymal stromal cells (allo-MSC) are a promising "off-the-shelf" therapy with anti-inflammatory and pro-repair properties. This study investigated humoral immune responses to intramuscular (IM) injections of allo-MSC. Total and isotype-specific anti-donor IgG and donor-specific complement-mediated lysis were determined in sera from healthy mice 2 weeks after single or repeated IM injections of fully mismatched-MHC allo-MSC with comparison to mice receiving syngeneic MSC, allogeneic splenocytes or saline. In mice subjected to hind limb ischemia (HLI), anti-donor IgG was analyzed following IM allo-MSC injection with and without administration of the T-cell immunosuppressant tacrolimus. Recipients of single and repeated IM allo-MSC developed readily-detectable anti-donor IgG. Serum anti-donor IgG levels were similar to those of allo-splenocyte recipients but had higher IgG1/IgG2a ratio and variable capacity for complement-mediated lysis of donor cells. The induced anti-donor IgG bound readily to allo-MSC and this binding was increased following allo-MSC pretreatment with interferon gamma. In mice with HLI, IM injection of allo-MSC into the ischemic limb was also associated with induction of anti-donor IgG but this was abrogated by tacrolimus (FK-506). The results indicate that allo-MSC are inherently immunogenic when delivered intramuscularly to healthy and ischemic mouse hind limb, but induce an IgG1-skewed humoral response that is suppressed by tacrolimus.

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Painting factor H onto mesenchymal stem cells protects the cells from complement- and neutrophil-mediated damage

Cited by 7 publications

References 38 publications

Stealth Immune Properties of Graphene Oxide Enabled by Surface-Bound Complement Factor H

Stealth Immune Properties of Graphene Oxide Enabled by Surface-Bound Complement Factor H

Allogeneic Mesenchymal Stromal Cells (MSCs) are of Comparable Efficacy to Syngeneic MSCs for Therapeutic Revascularization in C57BKSdb/db Mice Despite the Induction of Alloantibody

Anti‐donor antibody induction following intramuscular injections of allogeneic mesenchymal stromal cells

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