Anti-Inflammatory and Anti-Fibrotic Effects of Human Amniotic Membrane Mesenchymal Stem Cells and Their Potential in Corneal Repair

Abstract

Acute ocular chemical burns are ophthalmic emergencies requiring immediate diagnosis and treatment as they may lead to permanent impairment of vision. The clinical manifestations of such burns are produced by exacerbated innate immune response via the infiltration of inflammatory cells and activation of stromal fibroblasts. New therapies are emerging that are dedicated to repair mechanisms that improve the ocular surface after damage; for example, transplantation of stem cells (SC) has been successfully reported for this purpose. The pursuit of easily accessible, noninvasive procedures to obtain SC has led researchers to focus on human tissues such as amniotic membrane. Human amniotic mesenchymal SC (hAM‐MSC) inhibits proinflammatory and fibrotic processes in different diseases. hAM‐MSC expresses low levels of classical MHC‐I and they do not express MHC‐II, making them suitable for regenerative medicine. The aim of this study was to evaluate the effect of intracameral injection of hAM‐MSC on the clinical manifestations, the infiltration of inflammatory cells, and the activation of stromal fibroblasts in a corneal alkali‐burn model. We also determined the in vitro effect of hAM‐MSC conditioned medium (CM) on α‐SMA+ human limbal myofibroblast (HLM) frequency and on release of neutrophil extracellular traps (NETs). Our results show that intracameral hAM‐MSC injection reduces neovascularization, opacity, stromal inflammatory cell infiltrate, and stromal α‐SMA+ cells in our model. Moreover, in in vitro assays, CM from hAM‐MSC decreased the quantity of α‐SMA+ HLM and the release of NETs. These results suggest that intracameral hAM‐MSC injection induces an anti‐inflammatory and anti‐fibrotic environment that promotes corneal wound healing. Stem Cells Translational Medicine 2018;7:906–917

Cocktail of Hyaluronic Acid and Human Amniotic Mesenchymal Cells Effectively Repairs Cartilage Injuries in Sodium Iodoacetate-Induced Osteoarthritis Rats

“…They originate from the extra-embryonic mesoderm of the primitive streak, suggesting high cellular activity and differentiation capacity; they are capable of differentiating into chondrocytes in culture; and they have been identified to have similar phenotypes and characteristics to BMSCs, but with a stronger amplification and differentiation ability (Alviano et al, 2007;Ilancheran et al, 2007;Wei et al, 2009;Liu et al, 2016). They also exhibit non-immunogenicity and immunoregulatory activity, as well as an anti-fibrotic effect (Tsuno et al, 2012;Liu et al, 2016;Navas et al, 2018). Furthermore, they belong to the lineage of the mesoderm, the same germ layer as chondrocytes, and additionally, their resident environment, the amnion, is also a tissue without blood vessels, nerves, or lymphoid tissue, quite similar to the joint cartilage.…”

Comparison of amniotic membrane transplantation and carpal tunnel syndrome release surgery (CTRS) and CTRS alone: Clinical outcomes at 1‐year follow‐up

“…In this regard, we have previously shown that TSG‐6 secreted by human AM mesenchymal stem cells (hAM‐MSCs) is able to inhibit the activation of neutrophils; therefore, an inhibition at an early stage of the innate immune response could modulate an early improvement in CTS symptoms (Magana‐Guerrero, Dominguez‐Lopez, Martinez‐Aboytes, Buentello‐Volante, & Garfias, 2017). Also, conditioned medium from hAM‐MSC was able to downregulate the expression of α‐SMA in an acute ocular chemical burn model inhibiting corneal fibrosis; thus, the biomolecules secreted by AM cells might be able to inhibit perineural fibrosis, ameliorating CTS symptoms after CTRS (Navas et al, 2018). On the other hand, deepithelized AM exerted a selective caspase 3‐dependent apoptosis of the immune cells, while allowing epithelial cells to grow (Garfias et al, 2011); therefore, the effect of AM could be due to stromal matrix–nerve direct contact.…”

Biological approaches for hypertrophic scars

“…In atopic dermatitis, hMSCs were demonstrated the therapeutic functions in response to Th2 cytokines to mitigate dermatitis through suppressing MCs degranulation . In vitro, MSC was able to diminish human keratocyte differentiation into α‐SMA + limbal myofibroblast, and reduce the release of neutrophil extracellular traps, thus to promote corneal wound healing in an anti‐inflammatory and anti‐fibrotic way …”

“…197 In vitro, MSC was able to diminish human keratocyte differentiation into α-SMA + limbal myofibroblast, and reduce the release of neutrophil extracellular traps, thus to promote corneal wound healing in an anti-inflammatory and antifibrotic way. 198 Second, MSC can act on myofibroblasts, the main effector cells in HS formation. It was proved that bone marrow-derived MSCs inhibit myofibroblasts proliferation, migration, ECM synthesis, and scar formation through paracrine signalling.…”