Bone marrow is the traditional source of human multipotent mesenchymal stem cells (MSCs), but placenta appears to be an alternative and more readily available source. This study comprehensively compared human placenta–derived MSC (hpMSC) and human bone marrow–derived MSC (hbmMSC) in terms of cell characteristics, optimal growth conditions and in vivo safety specifically to determine if hpMSC could represent a source of human MSC for clinical trial. MSC were isolated from human placenta (hpMSC) and human bone marrow (hbmMSC) and expanded ex vivo using good manufacturing practice–compliant reagents. hpMSC and hbmMSC showed similar proliferation characteristics in different basal culture media types, fetal calf serum (FCS) concentrations, FCS heat-inactivation experiments, flask types and media replacement responsiveness. However, hpMSC and hbmMSC differed with respect to their proliferation capabilities at different seeding densities, with hbmMSC proliferating more slowly than hpMSC in every experiment. hpM...

Comparison of human placenta- and bone marrow-derived multipotent mesenchymal stem cells.

Neonatal hypoxia-ischaemia is the most common cause of death and disability in human neonates, and is often associated with persistent motor, sensory, and cognitive impairment. Improved intensive care technology has increased survival without preventing neurological disorder, increasing morbidity throughout the adult population. Early preventative or neuroprotective interventions have the potential to rescue brain development in neonates, yet only one therapeutic intervention is currently licensed for use in developed countries. Recent investigations of the transient cortical layer known as subplate, especially regarding subplate's secretory role, opens up a novel set of potential molecular modulators of neonatal hypoxiaischaemia injury. This review examines the biological mechanisms of human neonatal hypoxia-ischaemia, discusses evidence for the relevance of subplate-secreted molecules to this condition, and evaluates available animal models. Neuroserpin, a neuronally-released neuroprotective factor, is discussed as a case study for developing new potential pharmacological interventions for use post-ischaemic injury.

/pdf/neonatal-hypoxia-ischaemia-mechanisms-models-and-therapeutic-3h9d7lhxno.pdf

Neonatal Hypoxia Ischaemia: Mechanisms, Models, and Therapeutic Challenges

Our purpose was to compare healing characteristics of diabetic foot ulcers treated with dehydrated human amniotic membrane allografts (EpiFix®, MiMedx, Kennesaw, GA) versus standard of care. An IRB-approved, prospective, randomised, single-centre clinical trial was performed. Included were patients with a diabetic foot ulcer of at least 4-week duration without infection having adequate arterial perfusion. Patients were randomised to receive standard care alone or standard care with the addition of EpiFix. Wound size reduction and rates of complete healing after 4 and 6 weeks were evaluated. In the standard care group (n = 12) and the EpiFix group (n = 13) wounds reduced in size by a mean of 32·0% ± 47·3% versus 97·1% ± 7·0% (P < 0·001) after 4 weeks, whereas at 6 weeks wounds were reduced by −1·8% ± 70·3% versus 98·4% ± 5·8% (P < 0·001), standard care versus EpiFix, respectively. After 4 and 6 weeks of treatment the overall healing rate with application of EpiFix was shown to be 77% and 92%, respectively, whereas standard care healed 0% and 8% of the wounds (P < 0·001), respectively. Patients treated with EpiFix achieved superior healing rates over standard treatment alone. These results show that using EpiFix in addition to standard care is efficacious for wound healing.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/iwj.12097

A prospective randomised comparative parallel study of amniotic membrane wound graft in the management of diabetic foot ulcers

Comparison of immunomodulatory effects of placenta mesenchymal stem cells with bone marrow and adipose mesenchymal stem cells.

Introduction: This review presents the current in vitro and in vivo animal and human research on the roles of IL-8 in ocular inflammatory diseases.Materials and Methods: Data sources were a literature review using Pub Med, Medline, and ISI databases (from 1990 to 2011). Search items included interleukine-8 (IL-8), CXCL8, chemokines, cytokines, alone or in combination with the, serum, aqueous, vitreous, eye, ocular, ocular tissues, ophthalmic, and review.Results: IL-8 may be involved in primary or secondary ocular inflammations. Ocular effects of IL-8 differ based on the source of the secretion and site of the action. The most important effects of IL-8 in the eyes are angiogenic activities and induction of ocular inflammation.Conclusion: IL-8 plays important roles in ocular inflammation and angiogenesis in conjunctiva, cornea, iris, retina, and orbit. Anti-IL-8 targeted immunotherapy has been introduced as an important treatment modality, provided that IL-8 signal blocking takes place in desired areas and ...

Roles of IL-8 in ocular inflammations: a review.

Among the many cell types that may prove useful to regenerative medicine, mounting evidence suggests that human term placenta-derived cells will join the list of significant contributors. In making new cell therapy-based strategies a clinical reality, it is fundamental that no a priori claims are made regarding which cell source is preferable for a particular therapeutic application. Rather, ongoing comparisons of the potentiality and characteristics of cells from different sources should be made to promote constant improvement in cell therapies, and such comparisons will likely show that individually tailored cells can address disease-specific clinical needs. The principle underlying such an approach is resistance to the notion that comprehensive characterization of any cell type has been achieved, neither in terms of phenotype nor risks-to-benefits ratio. Tailoring cell therapy approaches to specific conditions also requires an understanding of basic disease mechanisms and close collaboration between translational researchers and clinicians, to identify current needs and shortcomings in existing treatments. To this end, the international workshop entitled "Placenta-derived stem cells for treatment of inflammatory diseases: moving toward clinical application" was held in Brescia, Italy, in March 2009, and aimed to harness an understanding of basic inflammatory mechanisms inherent in human diseases with updated findings regarding biological and therapeutic properties of human placenta-derived cells, with particular emphasis on their potential for treating inflammatory diseases. Finally, steps required to allow their future clinical application according to regulatory aspects including good manufacturing practice (GMP) were also considered. In September 2009, the International Placenta Stem Cell Society (IPLASS) was founded to help strengthen the research network in this field.

/pdf/toward-cell-therapy-using-placenta-derived-cells-disease-s33yv3b91a.pdf

Toward cell therapy using placenta-derived cells: disease mechanisms, cell biology, preclinical studies, and regulatory aspects at the round table.

Summary
Background The amniotic membrane (AM), which is the innermost layer of the placenta, was shown to possess anti-inflammatory and anti-fibrotic properties in various in vitro and clinical studies.

Purpose To evaluate the anti-fibrotic and anti-inflammatory effects of the AM matrix (AMM) on human conjunctival and lung fibroblasts in an in vitro system that tests fibrotic and inflammatory responses at the effector stages of allergic inflammation.

Methods Human conjunctival or lung fibroblasts were seeded on plastic or on the stromal aspect of the AM, which was mounted on plastic inserts. Sonicates of human peripheral blood eosinophils activated with lipopolysacharide (LPS), or human mast cell (HMC-1) leukaemia cell sonicates, were added to sub-confluent fibroblast monolayers. Proliferation of the sub-confluent fibroblasts was assessed using the [3H]-thymidine incorporation assay. The production of transforming growth factor (TGF)-β1, granulocyte–macrophage colony-stimulating factor (GM-CSF) and IL-8 in conjunctival or lung fibroblasts was measured in conditioned media from these cultures by ELISA.

Results After 4 days in culture, the [3H]-thymidine incorporation assay indicated a reduced proliferation of activated conjunctival and lung fibroblasts when cultured directly on the AMM. The production of both TGF-β1 and IL-8 was significantly suppressed in activated conjunctival fibroblasts cultured on the AMM compared with those cultured on plastic, while the production of both TGF-β1 and GM-CSF was decreased in human lung fibroblast cultured on the AMM.

Conclusions The AMM is capable of suppressing fibrotic responses in an in vitro system of effector stages of ocular allergic inflammation. These data may provide a basis for exploring matrix components in the AM for the treatment of allergic eye disease.

Suppression of inflammatory and fibrotic responses in allergic inflammation by the amniotic membrane stromal matrix.

Human term placenta as a therapeutic agent: from the first clinical applications to future perspectives

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Toward cell therapy using placenta-derived cells: disease mechanisms, cell biology, preclinical studies, and regulatory aspects at the round table.

Suppression of inflammatory and fibrotic responses in allergic inflammation by the amniotic membrane stromal matrix.

Human term placenta as a therapeutic agent: from the first clinical applications to future perspectives