Journal of Tissue Engineering and Regenerative Medicine最新文献

Despite the rising trend for applying platelet-rich plasma (PRP) in the management of various types of scars, there is no convincing evidence supporting its use. This motivated us to review the randomized clinical trials that examine the effectiveness and safety of PRP, alone or in combination with other methods, for the management of atrophic or hypertrophic/keloidal scars. The Web of Science, Scopus, Google Scholar, and Cochrane Library databases were systematically searched until September 1^st, 2020. Thirteen clinical trials were enrolled in the meta-analysis, and 10 more were reviewed for their results. The random effect meta-analysis method was used to assess the effect size of each outcome for each treatment type, and I² was used to calculate the statistical heterogeneity between the studies. Patients treated with PRP experienced an overall response rate of 23%, comparable to the results seen with laser or micro-needling (22% and 23%, respectively) When used alone, moderate improvement was the most frequently observed degree of response with PRP (36%) whereas, when added to laser or micro-needling, most patients experienced marked (33%, 43%, respectively) or excellent (32% and 23%, respectively) results. Concerning the hypertrophic/keloid scars, the only study meeting the required criteria reported a better improvement and fewer adverse effects when PRP was added to the intralesional corticosteroids. Platelet-rich plasma appears to be a safe and effective treatment for various types of atrophic scars. In addition, when added to ablative lasers or micro-needling, it seems to considerably add to the efficacy of treatment and reduce the side effects.

The high organ specification of the human heart is inversely proportional to its functional recovery after damage. The discovery of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) has accelerated research in human heart regeneration and physiology. Nevertheless, due to the immaturity of iPSC-CMs, they are far from being an representative model of the adult heart physiology. Therefore, number of laboratories strive to obtain a heart tissues by engineering methods by structuring iPSC-CMs into complex and advanced platforms. By using the iPSC-CMs and arranging them in 3D cultures it is possible to obtain a human heart muscle with physiological capabilities potentially similar to the adult heart, while remaining in vitro. Here, we attempt to describe existing examples of heart muscle either in vitro or ex vivo models and discuss potential options for the further development of such structures. This will be a crucial step for ultimate derivation of complete heart tissue-mimicking organs and their future use in drug development, therapeutic approaches testing, pre-clinical studies, and clinical applications. This review particularly aims to compile available models of advanced human heart tissue for scientists considering which model would best fit their research needs.

Orofacial mesenchymal stromal cells (OFMSCs) are mesenchymal stromal cells isolated from the oral and facial regions, which possess typical mesenchymal stromal cell features such as self-renewing, multilineage differentiation, and immunoregulatory properties. Recently, increasing studies have been carried out on the neurotrophic and neuroregenerative properties of OFMSCs as well as their potential to treat neurological diseases. In this review, we summarize the current evidence and discuss the prospects regarding the therapeutic potential of OFMSCs as a new approach to treat different neurological diseases and injuries.

A major challenge to the clinical translation of tissue-engineered ear scaffolds for ear reconstruction is the limited auricular chondrocyte (hAuC) yield available from patients. Starting with a relatively small number of chondrocytes in culture results in dedifferentiation and loss of phenotype with subsequent expansion. To significantly decrease the number of chondrocytes required for human elastic cartilage engineering, we co-cultured human mesenchymal stem cells (hMSCs) with HAuCs to promote healthy elastic cartilage formation. HAuCs along with human bone marrow-derived hMSCs were encapsulated into 1% Type I collagen at 25 million/mL total cell density with different ratios (HAuCs/hMSCs: 10/90, 25/75, 50/50) and then injected into customized 3D-printed polylactic acid (PLA) ridged external scaffolds, which simulate the shape of the auricular helical rim, and implanted subcutaneously in nude rats for 1, 3 and 6 months. The explanted constructs demonstrated near complete volume preservation and topography maintenance of the ridged “helical” feature after 6 months with all ratios. Cartilaginous appearing tissue formed within scaffolds by 3 months, verified by histologic analysis demonstrating mature elastic cartilage within the constructs with chondrocytes seen in lacunae within a Type II collagen and proteoglycan-enriched matrix, and surrounded by a neoperichondrial external layer. Compressive mechanical properties comparable to human elastic cartilage were achieved after 6 months. Co-implantation of hAuCs and hMSCs in collagen within an external scaffold efficiently produced shaped human elastic cartilage without volume loss even when hAuC comprised only 10% of the implanted cell population, marking a crucial step toward the clinical translation of auricular tissue engineering.

Menisci are fibrocartilaginous structures in the knee joint with an inadequate regenerative capacity, which causes low healing potential and further leads to osteoarthritis. Recently, three-dimensional (3D) printing techniques and ultrasound treatment have gained plenty of attention for meniscus tissue engineering. The present study investigates the effectiveness of low-intensity pulsed ultrasound stimulations (LIPUS) on the proliferation, viability, morphology, and gene expression of the chondrocytes seeded on 3D printed polyurethane scaffolds dip-coated with gellan gum, hyaluronic acid, and glucosamine. LIPUS stimulation was performed at 100, 200, and 300 mW/cm² intensities for 20 min/day. A faster gap closure (78.08 ± 2.56%) in the migration scratch assay was observed in the 200 mW/cm² group after 24 h. Also, inverted microscopic and scanning electron microscopic images showed no cell morphology changes during LIPUS exposure at different intensities. The 3D cultured chondrocytes under LIPUS treatment revealed a promotion in cell proliferation rate and viability as the intensity doses increased. Additionally, LIPUS could stimulate chondrocytes to overexpress the aggrecan and collagen II genes and improve their chondrogenic phenotype. This study recommends that the combination of LIPUS treatment and 3D hybrid scaffolds can be considered as a valuable treatment for meniscus regeneration based on our in vitro data.

Acute cardiac injuries occur in 20%–25% of hospitalized COVID-19 patients. Herein, we demonstrate that human cardiac organoids (hCOs) are a viable platform to model the cardiac injuries caused by COVID-19 hyperinflammation. As IL-1β is an upstream cytokine and a core COVID-19 signature cytokine, it was used to stimulate hCOs to induce the release of a milieu of proinflammatory cytokines that mirror the profile of COVID-19 cytokine storm. The IL-1β treated hCOs recapitulated transcriptomic, structural, and functional signatures of COVID-19 hearts. The comparison of IL-1β treated hCOs with cardiac tissue from COVID-19 autopsies illustrated the critical roles of hyper-inflammation in COVID-19 cardiac insults and indicated the cardioprotective effects of endothelium. The IL-1β treated hCOs thus provide a defined and robust model to assess the efficacy and potential side effects of immunomodulatory drugs, as well as the reversibility of COVID-19 cardiac injuries at baseline and simulated exercise conditions.

Spinal cord injury (SCI) can cause irreversible paralysis, with no regenerative treatment clinically available. Dogs with natural SCI present an established model and can facilitate translation of experimental findings in rodents to people. We conducted a prospective, single arm clinical safety study in companion dogs with chronic SCI to characterize the feasibility of intraspinal transplantation of hydrogel-encapsulated autologous mucosal olfactory ensheathing cell (mOEC) populations expressing chondroitinase ABC (chABC). mOECs and chABC are both promising therapies for SCI, and mOECs expressing chABC drive greater voluntary motor recovery than mOECs alone after SCI in rats. Canine mOECs encapsulated in collagen hydrogel can be matched in stiffness to canine SCI. Four dogs with complete and chronic loss of function caudal to a thoraco-lumbar lesion were recruited. After baseline measures, olfactory mucosal biopsy was performed and autologous mOECs cultured and transduced to express chABC, then hydrogel-encapsulated and percutaneously injected into the spinal cord. Dogs were monitored for 6 months with repeat clinical examinations, spinal MRI, kinematic gait and von Frey assessment. No adverse effects or significant changes on neurological examination were detected. MRI revealed large and variable lesions, with no spinal cord compression or ischemia visible after hydrogel transplantation. Owners reported increased pelvic-limb reflexes with one dog able to take 2–3 unsupported steps, but gait-scoring and kinematic analysis showed no significant improvements. This novel combination approach to regeneration after SCI is therefore feasible and safe in paraplegic dogs in a clinical setting. A randomised-controlled trial in this translational model is proposed to test efficacy.

Current rat model of rotator cuff (RC) tear could not mimic the suture anchor (SA) repair technique in the clinical practice. We designed a novel SA for RC repair of rats to establish a clinically relevant animal model. Small suture anchors that fit the rat shoulder were assembled. 60 rats were assigned to the transosseous (TO) repair group or SA repair group (n = 30/group). Micro-computed tomography (Micro-CT) scanning, biomechanical test and histological analysis were implemented at 2, 4, and 8-week post-repair. The failure load and stiffness in the SA group were significantly higher than those of TO group at 4-week post-repair. Micro-computed tomography analysis showed the bone mineral density and trabecular thickness of the SA group were significantly lower than those of TO group. The SA group showed a better insertion continuity at 4-week post-repair compared to TO group. No significant difference in gait parameters was found between groups. Therefore, SA repair is applicable for the rat model of RC tears. The SA repair achieved superior RC tendon healing, but more extensive initial bone damage compared to TO repair, while the shoulder function was comparable. This model could replicate the current repair technique in the clinical situation and be considered for future preclinical studies on healing enhancement for RC tears. Statement of Clinical Significance: With high clinical relevance, this model may facilitate the translation from an animal study into clinical trials.