Evaluation of Regenerative Efficacy of Amnion and Chorion Membrane in Treatment of Mandibular Molar Furcation Defects: A Clinico-radiographic Study.

AIM: Amnion and chorion membranes possess unique inherited biological properties that enhance wound healing and may accelerate periodontal regeneration. The present study aims to evaluate and compare the efficacy of amnion and chorion membranes in the treatment of furcation defects. MATERIALS AND METHODS: A total of 20 patients were selected and were randomly allocated to group I and group II with 10 subjects in each group. Amnion and chorion membranes are placental-derived membranes that accelerate regeneration by having natural growth factors with their antimicrobial and inflammation reduction properties. Group I was treated using bone grafting with decalcified freeze-dried bone allograft (DFDBA) and placement of amnion as a membrane for guided tissue regeneration (GTR) whereas group II was treated using bone grafting with DFDBA and placement of chorion as a membrane for GTR. The patients were followed for clinical and radiographic parameters and were evaluated between 3 and 6 months after surgery. RESULT: In intragroup comparison, a significant difference was evident in both the groups for all the clinical and radiographic parameters within the groups. (p = 0.01) This means both amnion and chorion membranes showed statistically significant regenerative efficacy. In intergroup comparison, the results show that all the clinical parameters and radiographic parameters show no significant difference between the groups. CONCLUSION: The amnion and chorion membranes had similar regenerative efficacy in combination with DFDBA in patients with buccal degree II furcation defects in mandibular molars. CLINICAL SIGNIFICANCE: The amnion and chorion membranes have shown significant improvement in clinical and radiographic parameters when used for the treatment of buccal degree II furcation defects in mandibular molars. How to cite this article: Mallapragda S, Gupta R, Gupta S, et al. Evaluation of Regenerative Efficacy of Amnion and Chorion Membrane in Treatment of Mandibular Molar Furcation Defects: A Clinico-radiographic Study. J Contemp Dent Pract 2024;25(2):160-167.

Dehydrated human amnion/chorion membrane to treat venous leg ulcers: a cost-effectiveness analysis.

OBJECTIVE: To evaluate the cost-effectiveness of dehydrated human amnion/chorion membrane (DHACM) in Medicare enrolees who developed a venous leg ulcer (VLU). METHOD: This economic evaluation used a four-state Markov model to simulate the disease progression of VLUs for patients receiving advanced treatment (AT) with DHACM or no advanced treatment (NAT) over a three-year time horizon from a US Medicare perspective. DHACM treatments were assessed when following parameters for use (FPFU), whereby applications were initiated 30-45 days after the initial VLU diagnosis claim, and reapplications occurred on a weekly to biweekly basis until completion of the treatment episode. The cohort was modelled on the claims of 530,220 Medicare enrolees who developed a VLU between 2015-2019. Direct medical costs, quality-adjusted life years (QALYs), and the net monetary benefit (NMB) at a willingness-to-pay threshold of $100,000/QALY were applied. Univariate and probabilistic sensitivity analyses (PSA) were performed to test the uncertainty of model results. RESULTS: DHACM applied FPFU dominated NAT, yielding a lower per-patient cost of $170 and an increase of 0.010 QALYs over three years. The resulting NMB was $1178 per patient in favour of DHACM FPFU over the same time horizon. The rate of VLU recurrence had a notable impact on model uncertainty. In the PSA, DHACM FPFU was cost-effective in 63.01% of simulations at the $100,000/QALY threshold. CONCLUSION: In this analysis, DHACM FPFU was the dominant strategy compared to NAT, as it was cost-saving and generated a greater number of QALYs over three years from the US Medicare perspective. A companion VLU Medicare outcomes analysis revealed that patients who received AT with a cellular, acellular and matrix-like product (CAMP) compared to patients who received NAT had the best outcomes. Given the added clinical benefits to patients at lower cost, providers should recommend DHACM FPFU to patients with VLU who qualify. Decision-makers for public insurers (e.g., Medicare and Medicaid) and commercial payers should establish preferential formulary placement for reimbursement of DHACM to reduce budget impact and improve the long-term health of their patient populations dealing with these chronic wounds. DECLARATION OF INTEREST: Support for this analysis was provided by MiMedx Group, Inc., US. JLD, and RAF are employees of MiMedx Group, Inc. WHT, BH, PS, BGC and WVP were consultants to MiMedx Group, Inc. VD, AO, MRK, JAN, NW and GAM served on the MiMedx Group, Inc. Advisory Board. MRK and JAN served on a speaker's bureau. WVP declares personal fees and equity holdings from Stage Analytics, US.

Membrane inflammasome activation by choriodecidual Ureaplasma parvum infection without intra-amniotic infection in a Non-Human Primate model†.

Intrauterine infection is a significant cause of neonatal morbidity and mortality. Ureaplasma parvum is a microorganism commonly isolated from cases of preterm birth and preterm premature rupture of membranes (pPROM). However, the mechanisms of early stage ascending reproductive tract infection remain poorly understood. To examine inflammation in fetal (chorioamnionic) membranes we utilized a non-human primate (NHP) model of choriodecidual U. parvum infection. Eight chronically catheterized pregnant rhesus macaques underwent maternal-fetal catheterization surgery at ~105-112 days gestation and choriodecidual inoculation with U. parvum (105 CFU/mL, n =4) or sterile media (controls; n = 4) starting at 115-119 days, repeated at 5-day intervals until C-section at 136-140 days (term=167 days). The average inoculation to delivery interval was 21 days, and Ureaplasma infection of the amniotic fluid (AF) was undetectable in all animals. Choriodecidual Ureaplasma infection resulted in increased fetal membrane expression of MMP-9 and PTGS2, but did not result in preterm labor or increased concentrations of AF pro-inflammatory cytokines. However, membrane expression of inflammasome sensors, NLRP3, NLRC4, AIM2, and NOD2, and adaptor ASC (PYCARD) gene expression were significantly increased. Gene expression of IL-1ß, IL-18, IL-18R1  , CASPASE-1, and pro-CASPASE-1 protein increased with Ureaplasma infection. Downstream inflammatory genes MYD88 and NFκB (Nuclear factor kappa-light-chain-enhancer of activated B cells) were also significantly upregulated. These results demonstrate that choriodecidual Ureaplasma infection, can cause activation of inflammasome complexes and pathways associated with pPROM and preterm labor prior to microbes being detectable in the AF.

Unique Usages of Dehydrated Human Amnion Chorion Membrane Allografts in Dermatology.

Dehydrated human amnion chorion membrane (dHACM) allografts are synthetic skin substitutes derived from placental tissue. dHACM allografts are used for replacing lost or damaged dermal tissue, as they contain many of the components found within the extracellular matrix that are beneficial in wound healing. Common uses of dHACM allografts include the healing of diabetic and non-diabetic foot and leg ulcers, decubitus ulcers, and wounds following debridement. While these grafts have been proven to be beneficial in other disciplines of medicine, their potential for use in the field of dermatology is emerging. Current clinical cases and research have shown dHACM allografts to be beneficial in repairing damaged tissue due to dermatologic conditions. They could play a role in the treatment of conditions causing chronic wounds, including dermal scarring or loss, and the repair of fragile skin. Examples of dHACM allograft use in dermatology include cases of pyoderma gangrenosum, Netherton syndrome, and wound healing with Mohs micrographic surgery. This literature review explores the efficacy of using dHACM allografts for the treatment of healing wounds within the field of dermatology. J Drugs Dermatol. 2023;22(12):1228-1231. doi:10.36849/JDD.7115.

Dehydrated human amnion/chorion membrane use in emergent craniectomies shows minimal dural adhesions.

Decompressive craniectomies (DCs) are routinely performed neurosurgical procedures to emergently treat increased intracranial pressure secondary to multiple aetiologies, such as subdural haematoma, epidural haematoma, or malignant oedema in the setting of acute infarction. The DC procedure typically induces epidural fibrosis post-cranial resection, resulting in adherence of the dura to both the brain internally and skin flap externally. This becomes especially problematic in the setting of skull flap replacement for cranioplasty as adherences can lead to bridging vein tear, damage to the underlying brain cortex, and other postoperative complications. Dural adjuvants, which can contribute to decreased rate of adherence formation, can thereby reduce both postoperative cranioplasty complications and operative duration. Dehydrated human amnion/chorion membrane (DHACM) allografts (AMNIOFIX, MIMEDX Group Inc., US) have been shown to reduce the rate of dural scar tissue formation in re-exploration of posterior lumbar interbody fusion operations which require entry into the epidural space. The purpose of this study was to evaluate whether or not the use of DHACM in the setting of emergent craniectomies decreased the rate of dural adhesion formation and subsequent cranioplasty complications. Patients (n=7) who underwent emergent craniectomy and intraoperative placement of DHACM were evaluated during replacement of either an autologous skull cap or a custom-made implant, at which point the degree of adhesions was qualitatively assessed. Placement of DHACM below and on top of the dura resulted in negligible adhesion being found during the defect exposure, and there were no intraoperative complications during cranioplasties. Reported estimated blood loss across the seven patients averaged 64.2ml, total operative time averaged 79.2 minutes, and time dedicated to exposing defect for bone flap placement was <3 minutes.

Ruptura prematura de membranas ovulares / Premature rupture of ovular membranes

La ruptura prematura de las membranas ovulares se define como la pérdida de la integridad del amnios y corion antes del inicio del trabajo de parto, afecta el 3 % de los embarazos, causa un tercio de los partos pretérminos, los cuales ocupan el 10,49 % de los nacimientos y es el origen de altos índices de morbimortalidad perinatal. En la actualidad, el manejo de esta patología se orienta principalmente en evitar los factores de riesgo, hacer un diagnóstico adecuado, determinar la edad gestacional en que ocurre, realizar el monitoreo exhaustivo del bienestar materno-fetal y en decidir el momento idóneo de finalización de la gestación para minimizar sus complicaciones. Debido a la compleja y lábil estructura histológica de las membranas ovulares, se ha dejado a un lado el tratamiento directo de la entidad el cual sería sellar o reparar el defecto en sí. En los últimos años, numerosos estudios y protocolos clínicos de prestigiosos centros asistenciales han servido como guía para el manejo de esta entidad, pero en muy pocos se observa una terapia destinada a la reparación de dichas membranas o en sellar tal defecto. Las evidencias científicas demuestran que la regeneración y reparación de las membranas es lenta y compleja y los tratamientos propuestos para reparar o sellar su defecto no han gozado de la aceptación científica para su aprobación, sin embargo, el uso del parche hemático transvaginal endocervical autólogo luce como una alternativa terapéutica prometedora(AU)

The premature rupture of the ovular membranes is defined as the loss of the integrity of the amnion and chorion before the on set of labor, affects 3% of pregnancies, causes athird of preterm births which occupy 10,49% of births and is the origin of high rates of perinatal morbidity and mortality. At present, the management of this pathology is mainly oriented towards avoiding risk factors, making an adequate diagnosis, determining the gestational age in which it occurs, carrying out exhaustive monitoring of maternal-fetal well-being and deciding the ideal moment to end the treatment. Pregnancy to minimizeits complications. Due to the complex and labile histological structure of the ovular membranes, the direct treatment of the entity has been set a side, which would be to seal or repairthe defect it self. In recent years, numerous studies and clinicalprotocols from prestigious health care centers have served as aguide for the management of this entity, but very few have observed a therapy aimed at repairing said membranes or sealing such a defect. Scientific evidence shows that the regeneration and repair of the membranes is slow and complex and the treatment sproposed to repair or seal their defect have not enjoyed scientific acceptance for their approval, how ever, the use of the autologous endocervical transvaginal blood patch looks like a promising therapeutic alternative(AU)

The Placenta in Congenital Langerhans Cell Histiocytosis: A Case Report of Unusual Involvement of Chorionic Plate and Umbilical Vein.

The congenital presentation of Langerhans cell histiocytosis (LCH) is a rare presentation of an uncommon neoplastic process. Concurrent placental parenchymal involvement is even more rare, with just 2 cases of congenital multisystem LCH with placental involvement reported in English medical literature thus far. Here, we present a case of a liveborn male born at 37-weeks, 6-day gestation with congenital LCH focally involving the placenta. Langerhans cells were identified in an area of the placenta showing an unusual mononuclear cell infiltrate in the wall of the umbilical vein. Langerhans cells were also focally identified in areas of chronic villitis, as well as normal-appearing chorionic plate. The examination of the placenta in cases of clinical suspicion of LCH can be of paramount importance since it may provide the early diagnostic evidence of LCH. In this context, placental involvement by LCH should be considered even in the absence of abnormal histology.

Treatment of Gingival Recession Defects with Pouch and Tunnel Technique Using Connective Tissue Graft and Lyophilized Chorion Membrane in Smokers.

BACKGROUND The chorion membrane has been used for several decades as an allograft in tissue repair and various periodontal regenerative procedures. The present study, conducted at a single center in India, aimed to evaluate and compare the clinical outcomes of 26 gingival recession sites in chronic smokers treated using a pouch and tunnel technique with connective tissue graft (CTG) and lyophilized chorion membrane (LCM). MATERIAL AND METHODS The study included 22 smokers with 26 sites of recession defect, with Miller's class I and class II gingival recession, which were allotted into control and test groups. The control group (13 sites) was treated with CTG, and the test group (13 sites) was treated with LCM. Clinical parameters like recession depth, recession width, relative clinical attachment level (RCAL), relative gingival position, width of attached gingiva, and width of keratinized gingiva were recorded at baseline and 6 months postoperatively. Visual analogue scores for pain and wound-healing index scores were assessed in the first week after surgery. RESULTS All clinical parameters showed significant improvements from baseline to 6 months postoperatively in the control and test groups. Recession width, RCAL, width of attached gingiva, and width of keratinized gingiva demonstrated significant differences, whereas mean root coverage percentage and recession depth did not show any significant differences between the study groups at 6 months postoperatively. CONCLUSIONS This study supports the role of LCM allograft as a scaffold to promote soft tissue regeneration and has demonstrated a favorable role for its use in root coverage procedures in patients who smoke.

The chick embryo chorioallantoic membrane patient-derived xenograft (PDX) model.

The chick embryo chorioallantoic membrane (CAM) CAM is an extraembryonic membrane generated by the fusion of the chorion with the vascularized allantoic membrane. It performs multiple functions during embryonic development, including respiration, calcium transport from the eggshell, acid-base homeostasis, and ion/water reabsorption from the allantoic fluid. The CAM is a widely used model for the study of angiogenesis, anti-angiogenesis, tumor growth, and metastasis as well as drug efficacy. Ethical approval is omitted if experiments are terminated at embryonic day 14 in most countries, facilitating screenings of pharmacological or physics-based therapies with high reproducibility at large scales supporting the 3Rs principle. Being naturally immunodeficient, the chick embryo accepts transplantation from various tissues and species without immune response. This review article is focused on the analysis of the literature and personal data concerning the effects of patient-derived xenografts (PDX) on the CAM.

Mesothelial fusion mediates chorioallantoic membrane formation.

In amniotic vertebrates (birds, reptiles and mammals), an extraembryonic structure called the chorioallantoic membrane (CAM) functions as respiratory organ for embryonic development. The CAM is derived from fusion between two pre-existing membranes, the allantois, a hindgut diverticulum and a reservoir for metabolic waste, and the chorion which marks the embryo's external boundary. Modified CAM in eutherian mammals, including humans, gives rise to chorioallantoic placenta. Despite its importance, little is known about cellular and molecular mechanisms mediating CAM formation and maturation. In this work, using the avian model, we focused on the early phase of CAM morphogenesis when the allantois and chorion meet and initiate fusion. We report here that chicken chorioallantoic fusion takes place when the allantois reaches the size of 2.5-3.0 mm in diameter and in about 6 hours between E3.75 and E4. Electron microscopy and immunofluorescence analyses suggested that before fusion, in both the allantois and chorion, an epithelial-shaped mesothelial layer is present, which dissolves after fusion, presumably by undergoing epithelial-mesenchymal transition. The fusion process per se, however, is independent of allantoic growth, circulation, or its connection to the developing mesonephros. Mesoderm cells derived from the allantois and chorion can intermingle post-fusion, and chorionic ectoderm cells exhibit a specialized sub-apical intercellular interface, possibly to facilitate infiltration of allantois-derived vascular progenitors into the chorionic ectoderm territory for optimal oxygen transport. Finally, we investigated chorioallantoic fusion-like process in primates, with limited numbers of archived human and fresh macaque samples. We summarize the similarities and differences of CAM formation among different amniote groups and propose that mesothelial epithelial-mesenchymal transition mediates chorioallantoic fusion in most amniotic vertebrates. Further study is needed to clarify tissue morphogenesis leading to chorioallantoic fusion in primates. Elucidating molecular mechanisms regulating mesothelial integrity and epithelial-mesenchymal transition will also help understand mesothelial diseases in the adult, including mesothelioma, ovarian cancer and fibrosis. This article is part of the theme issue 'Extraembryonic tissues: exploring concepts, definitions and functions across the animal kingdom'.

A Multicenter, Randomized, Controlled, Clinical Trial Evaluating Dehydrated Human Amniotic Membrane in the Treatment of Venous Leg Ulcers.

BACKGROUND: This randomized controlled trial evaluated the safety and effectiveness of weekly and biweekly applications of dehydrated human amnion and chorion allograft (dHACA) plus standard of care compared to standard of care alone on chronic venous leg ulcers. METHODS: This open-label randomized controlled trial included patients with chronic venous leg ulcers at eight wound care centers across the United States. The primary endpoint was the proportion of healed ulcers at 12 weeks. Secondary endpoints included the proportion of ulcers achieving 40 percent closure at 4 weeks and the incidence of adverse events. RESULTS: Among 101 patients screened for eligibility, 60 were eligible and enrolled. At 12 weeks, significantly more venous leg ulcers healed in the two dHACA-treated groups (75 percent) than in the standard-of-care group (30 percent) ( p = 0.001) even after adjustment for wound area ( p = 0.002), with an odds ratio of 8.7 (95 percent CI, 2.2 to 33.6). There were no significant differences in the proportion of wounds with percentage area reduction greater than or equal to 40 percent at 4 weeks among all groups. The adverse event rate was 63.5 percent. Among the 38 adverse events, none were graft or procedure related, and all were resolved with appropriate treatment. CONCLUSIONS: dHACA and standard of care, either applied weekly or biweekly, significantly healed more venous leg ulcers than standard of care alone, suggesting that the use of aseptically processed dHACA is advantageous and a safe and effective treatment option in the healing of chronic venous leg ulcers. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

cAMP Response Element-Binding Protein Controls the Appearance of Neuron-Like Traits in Chorion Mesenchymal Cells.

BACKGROUND: Mesenchymal stromal cells (MSC) from bone marrow have been reported to undergo the initial phases of neural differentiation in response to an increase of intracellular cAMP. We investigated the possibility that a similar effect applies to chorion-derived MSC. METHODS: The intracellular concentration of cAMP was increased either by forskolin, to promote its synthesis, or by inhibitors of its degradation. The consequent reduction in the expression of mesenchymal markers was associated with the appearance of neuron-like morphology in a subset of cells. The effect was measured and characterized using biomarkers and an inhibitor of cAMP response element-binding protein (CREB). RESULTS: The dramatic morphological change induced by all the treatments that promoted intracellular cAMP was transient and peaked on the third day. After that, cells returned to the typical fibroblast-like appearance within 24 hours. The distinctive morphology was associated to the expression of neuregulin 1, doublecortin, neuron-specific class III ß-tubulin, and required cAMP response element-binding protein activity. Basic-fibroblast growth factor (b-FGF) treatment increased both the timeframe and number of cells undergoing the morphological change induced by the effect of forskolin. As opposite, arginine-vasopressin (AVP) and sphingosine-1-phosphate (S1P) reduced it. CONCLUSIONS: We conclude that cAMP and the ensuing CREB activation trigger a preliminary step towards neuronal differentiation of chorion-derived MSC. However, likewise other MSC, the stimulus is not sufficient to promote stable differentiation.

Human chorion-derived mesenchymal stem cells suppress JAK2/STAT3 signaling and induce apoptosis of cholangiocarcinoma cell lines.

Cholangiocarcinoma (CCA) is an aggressive malignancy arising from the damaged epithelial cells of the biliary tract. Previous studies have reported that the multi-potent mesenchymal stem cells (MSCs) activate a series of tumor signaling pathways by releasing several cytokines to influence tumor cell development. However, the roles and mechanisms of human chorion-derived MSCs (CH-MSCs) in cholangiocarcinoma progression have not been fully addressed. This present study aims to examine the effects of conditioned media derived from CH-MSCs (CH-CM) on CCA cell lines and investigate the respective underlying mechanism of action. For this purpose, MSCs were isolated from chorion tissue, and three cholangiocarcinoma cell lines, namely KKU100, KKU213A, and KKU213B, were used. MTT assay, annexin V/PI analysis, and JC-1 staining were used to assess the effects of CH-CM on proliferation and apoptosis of CCA cells, respectively. Moreover, the effect of CH-CM on caspase-dependent apoptotic pathways was also evaluated. The western blotting assay was also used for measuring the expression of JAK2/STAT3 signaling pathway-associated proteins. The results showed that CH-CM suppressed proliferation and promoted apoptosis of CCA cell lines. CH-CM treatment-induced loss of mitochondrial membrane potential (∆Ψm) in CCA cell lines. The factors presented in the CH-CM also inhibited JAK2/STAT3 signaling, reduced the expression of BCL-2, and increased BAX expression in CCA cells. In conclusion, our study suggests that the CH-CM has a potent anti-cancer effect on cholangiocarcinoma cells and thus provides opportunities for use in alternative cell therapy or in combination with a conventional chemotherapeutic drug to increase the efficiency of CCA treatment.

Investigating the Effects of Dehydrated Human Amnion-Chorion Membrane on Periodontal Healing.

Each growth factor (GF) has different effects and targets, and plays a critical role in periodontal healing. Dehydrated human amnion-chorion membrane (dHACM) contains various GFs and has been used to enhance wound healing. The purpose of this study was to evaluate the effects of dHACM on periodontal healing, using in vitro and in vivo experimental approaches. Standardized periodontal defects were created in rats. The defects were randomly divided into three groups: Unfilled, filled with hydroxypropyl cellulose (HPC), and dHACM+HPC. At 2 and 4 weeks postoperatively, periodontal healing was analyzed by microcomputed tomography (micro-CT), and histological and immunohistochemical analyses. In vitro, periodontal ligament-derived cells (PDLCs) isolated from rat incisors were incubated with dHACM extract. Cell proliferation and migration were evaluated by WST-1 and wound healing assay. In vivo, micro-CT examination at 2 weeks revealed enhanced formation of new bone in the dHACM+HPC group. At 4 weeks, the proportions of vascular endothelial growth factor (VEGF)-positive cells and α-smooth muscle actin (α-SMA)-positive blood vessels in the dHACM+HPC group were significantly greater than those in the Unfilled group. In vitro, dHACM extracts at 100 µg/mL significantly increased cell proliferation and migration compared with control. These findings suggest that GFs contained in dHACM promote proliferation and migration of PDLCs and angiogenesis, which lead to enhanced periodontal healing.

Title-comparison of coronally advanced flap with chorion membrane vs coronally advanced flap with connective tissue graft in the treatment of multiple gingival recessions: a split-mouth randomised controlled study.

Background: The importance of esthetics has escalated over the years. The purpose of any perioplastic surgery is to address gingival recession while ensuring predictable root coverage and a pleasing appearance. An array of surgical procedures have been recommended for the management of recession defects. The present study compares the clinical and patient related outcome measures of coronally advanced flap with chorion membrane and connective tissue graft in the management of multiple adjacent gingival recessions. Methods: The study was a prospective randomized controlled trial which included eight systemically healthy patients with an age range of 30-44 years with 36 labial/buccal, multiple adjacent, Cairo's RT1 gingival recession defects, bilaterally.  CAF+CM was performed on one side whereas CAF+CTG was performed on the other side. The two groups were compared clinically at three and six months postoperatively. Results: There was statistically significant decrease in recession depth, recession width, probing depth and clinical attachment level in both the groups from baseline to three and six months. However, intergroup comparisons revealed no statistically significant difference. At six months, both groups showed statistically significant improvements in keratinized tissue width and gingival thickness. The gingival thickness of the CAF+CM group increased significantly at three and six months. In terms of root coverage aesthetic score (RES), there was no significant difference observed between the two groups. In terms of patient reported outcome measures (PROMS), patients preferred the CAF+CM technique. Conclusion: Within the limits of the current study, the use of chorion membrane resulted in considerable root coverage and increased gingival thickness. Periodontal regeneration can be facilitated by the distinctive features of the chorion membrane. Coronally advanced flap plus chorion membrane is a novel approach for root coverage procedures.

Chorion-derived perinatal mesenchymal stem cells improve cardiac function and vascular regeneration: Preferential treatment for ischemic heart disease.

BACKGROUND: Stem cell therapy has emerged as a novel treatment for heart failure after myocardial infarction (Ml). Bone marrow-derived mesenchymal stem cells (BM-MSCs) are commonly considered because of their accessibility and usability. However, their therapeutic potential remains controversial. In our previous in vitro study, chorion-derived mesenchymal stem cells (C-MSCs) and umbilical cord-derived mesenchymal stem cells (UC-MSCs) demonstrated an ability to differentiate into cardiomyocytes and neural cells, respectively. Thus, we examined whether C-MSCs had a better differentiation potential in an MI animal model. METHODS: MI was induced by ligation of the left anterior descending artery, and DiI-labeled MSCs were injected into the border of the infarcted myocardium. The left ventricular ejection fraction (LVEF) and fractional shortening (FS) were measured using echocardiograms. Masson's Trichrome staining was performed to evaluate the viable myocardium. Alpha-sarcomeric actin (α-SA), cardiac troponin-T (cTnT), and isolectin were immunolabeled to evaluate differentiation and capillary formation. RESULTS: After 8 weeks, the LVEF and FS significantly increased to a greater extent in the C-MSC-injected group with maintenance of viable myocardium, as compared to in the control, UC-MSC-, and BM-MSC-injected groups (p < 0.05). Compared to UC-MSCs and BM-MSCs, C-MSCs significantly increased the capillary density (p < 0.05) and demonstrated higher expressions of cTnT and α-SA. CONCLUSIONS: In conclusion, compared to UC-MSCs and BM-MSCs, C-MSCs showed a better therapeutic efficacy in a rat MI model.

Study of mesenchymal stem cells derived from lung-resident, bone marrow and chorion for treatment of LPS-induced acute lung injury.

BACKGROUND: Mesenchymal stem cells (MSCs) have been shown to improve acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). However, the optimal source of MSCs for cell-based therapy remains unknown. To determine which kind of MSCs are more effective, we compared the effects of rat lung resident MSC (LRMSC), human chorion-derived MSC (HMSC-C) and human bone marrow derived MSC (HMSC-BM) in LPS-induced ALI in mice. METHODS: LPS (Pseudomonas aeruginosa) was used to induce ALI model. All three kinds of MSCs were administered via tail vein 4 h after LPS instillation. The mice were sacrificed 48 h after LPS instillation. H&E staining of lung section, wet-to-dry weight ratio of lung tissue, ratio of regulatory T cells (Tregs) and Th17 cells, and total protein concentration, leukocytes counting and cytokines in bronchoalveolar lavage fluid (BALF) were evaluated. RESULTS: The data showed that compared with LRMSC and HMSC-BM, HMSC-C more significantly attenuated lung injury, upregulated the Tregs/Th17 cells ratio, and inhibited release of inflammatory cytokines (IL-1ß, IL-6 and TNF-α) and recruitment of neutrophils and macrophages into alveolus. CONCLUSIONS: Although all three kinds of LRMSC, HMSC-C and HMSC-BM are protective against LPS-induced lung injury, HMSC-C was more effective than LRMSC and HMSC-BM to treat LPS-induced lung injury.

Wound repair, safety, and functional outcomes in reconstructive lower extremity foot and ankle surgery using a dehydrated amnion/chorion allograft membrane.

Amniotic membranes are known to be rich in growth factors, cytokines, and matrix proteins, which can help support wound closure and may improve patient outcomes in foot and ankle surgical interventions. In this Institutional Review Board (IRB) approved clinical study, 21 consecutive patients undergoing lower extremity soft tissue and bone reconstruction surgery received dehydrated human amnion and chorion allograft (dHACA) placed as a covering over the deep layers of the surgical wound during closure. Wound healing complications were assessed and American Orthopaedic Foot and Ankle Society (AOFAS) scores were compiled from over a 1-year follow-up period. Summary statistics were calculated for average pain, function, and alignment. The average overall AOFAS pre-treatment score was 35.8 ± 23.0 and the post-treatment score significantly improved to 87.5 ± 6.4 (P = 3.7 × 10-10 ). The pain-score improved from pre-treatment at 10.0 ± 11.0 to post-treatment at 36.7 ± 4.8 (P = 5.0 × 10-5 ). The pre-treatment function score was 18.7 ± 12.9 and at post-treatment increased to 38.5 ± 5.7 (P = 5.8 × 10-5 ). Lastly, the alignment score at pre-treatment was 7.1 ± 4.4 and at post-treatment was 12.4 ± 2.6 (P = .001). These improvements in functional scores were accompanied with clinical observations of reduced surgical complications including a lack of wound dehisance in the cohort. These clinical findings suggest that the application of aseptically processed dHACA may reduce wound complications and as such may aide in clinical improvements in foot and ankle surgical interventions however a larger comparative trial should be considered to validate these initial findings.

Routing pathway of syngeneic donor hematopoietic stem cells after simple intra-amniotic delivery.

BACKGROUND: We sought to determine the pathway through which syngeneic hematopoietic stem cells (HSCs) delivered into the amniotic fluid can reach the fetal circulation. METHODS: Lewis rat fetuses were divided in two groups based on the content of intra-amniotic injections performed on gestational day 17 (E17; term=E21-22): either a suspension of luciferase-labeled syngeneic HSCs (n = 137), or acellular luciferase (n = 44). Samples from placenta, chorion, amnion, amniotic fluid, umbilical cord, and 8 fetal sites were procured at 5 daily time points thereafter until term for analysis. RESULTS: When controlled by acellular luciferase, donor HSCs were identified in the amnion, chorion, placenta, and amniotic fluid of fetuses receiving cells at all time points (p = 0.033 to <0.001), peaking first at the amnion and subsequently at the chorion and placenta. Cells could be detected in the fetal liver as early as day 1, progressively expanding to all the other fetal sites over time, in parallel to their increased presence in the chorion and placenta. CONCLUSIONS: The chronology of syngeneic donor hematopoietic stem cell trafficking after intra-amniotic injection is suggestive of controlled routing through the gestational membranes and placenta. Hematogenous donor cell routing is a constituent of transamniotic hematopoietic stem cell therapy, significantly expanding its potential applications.

Human Amnion/Chorion Membrane May Reduce Transient Recurrent Laryngeal Nerve Injury During Thyroid Surgery.

Recurrent laryngeal nerve (RLN) damage is a significant and prevalent complication of thyroid surgery. Based on the beneficial role of a human amnion/chorion membrane (HACM) allograft in wound management and nerve regeneration, we investigated whether placement of a commercially available HACM allograft on dissected RLN could reduce the occurrence and/or duration of RLN injury during thyroidectomy. Among 67 patients undergoing thyroidectomy, 100 at-risk nerves (exposure of at least 3 cm of RLN) received intraoperative placement of HACM; 205 at-risk RLNs without HACM in 134 matched patients served as controls. Patient-reported vocal analysis, physician-assessed vocal analysis, and laryngoscopic assessment of vocal-fold dysfunction were performed before and after surgery. At 24 h after surgery, 17 patients in the control group (12.5%) had documented voice changes; these changes persisted for at least 3 weeks in seven patients (5%). Only one patient (1.5%) in the HACM group had vocal changes at 24 h after surgery, which resolved within 1 week (P < 0.01). Intraoperative placement of the HACM allograft over at-risk RLNs during thyroidectomy may reduce the incidence, severity, and/or duration of intraoperative RLN injury, which could address a significant complication of head and neck surgery. A larger prospectively designed clinical study is warranted to further investigate a possible benefit of the HACM allograft in thyroid surgery and to begin to understand the mechanisms through which a clinical benefit might be mediated.