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Regenerative therapy

Oriane Blanquie, Frank Bradke
Recent years have seen cytoskeleton dynamics emerging as a key player in axon regeneration. The cytoskeleton, in particular microtubules and actin, ensures the growth of neuronal processes and maintains the singular, highly polarized shape of neurons. Following injury, adult central axons are tipped by a dystrophic structure, the retraction bulb, which prevents their regeneration. Abnormal cytoskeleton dynamics are responsible for the formation of this growth-incompetent structure but pharmacologically modulating cytoskeleton dynamics of injured axons can transform this structure into a growth-competent growth cone...
March 12, 2018: Current Opinion in Neurobiology
Bingbo Zhang, Wei Yan, Yanjing Zhu, Weitao Yang, Wenjun Le, Bingdi Chen, Rongrong Zhu, Liming Cheng
Patients are increasingly being diagnosed with neuropathic diseases, but are rarely cured because of the loss of neurons in damaged tissues. This situation creates an urgent clinical need to develop alternative treatment strategies for effective repair and regeneration of injured or diseased tissues. Neural stem cells (NSCs), highly pluripotent cells with the ability of self-renewal and potential for multidirectional differentiation, provide a promising solution to meet this demand. However, some serious challenges remaining to be addressed are the regulation of implanted NSCs, tracking their fate, monitoring their interaction with and responsiveness to the tissue environment, and evaluating their treatment efficacy...
March 15, 2018: Advanced Materials
Maria E Piroli, Ehsan Jabbarzadeh
Human stem cells hold significant potential for the treatment of various diseases. However, their use as a therapy is hampered because of limited understanding of the mechanisms by which they respond to environmental stimuli. Efforts to understand extracellular biophysical cues have demonstrated the critical roles of geometrical and mechanical signals in determining the fate of stem cells. The goal of this study was to explore the interplay between cell polarity and matrix stiffness in stem cell lineage specification...
March 14, 2018: Annals of Biomedical Engineering
Shantisree Sandeepani Rayagiri, Daniele Ranaldi, Alexander Raven, Nur Izzah Farhana Mohamad Azhar, Olivier Lefebvre, Peter S Zammit, Anne-Gaëlle Borycki
A central question in stem cell biology is the relationship between stem cells and their niche. Although previous reports have uncovered how signaling molecules released by niche cells support stem cell function, the role of the extra-cellular matrix (ECM) within the niche is unclear. Here, we show that upon activation, skeletal muscle stem cells (satellite cells) induce local remodeling of the ECM and the deposition of laminin-α1 and laminin-α5 into the basal lamina of the satellite cell niche. Genetic ablation of laminin-α1, disruption of integrin-α6 signaling or blocking matrix metalloproteinase activity impairs satellite cell expansion and self-renewal...
March 14, 2018: Nature Communications
Gary Hin-Fai Yam, Ericia Pei-Wen Teo, Melina Setiawan, Matthew J Lovatt, Nur Zahirah Binte M Yusoff, Matthias Fuest, Bee-Tin Goh, Jodhbir S Mehta
Corneal opacities are a leading cause of global blindness. They are conventionally treated by the transplantation of donor corneal tissue, which is, restricted by a worldwide donor material shortage and allograft rejection. Autologous adult stem cells with a potential to differentiate into corneal stromal keratocytes (CSKs) could offer a suitable choice of cells for regenerative cell therapy. Postnatal periodontal ligament (PDL) contains a population of adult stem cells, which has a similar embryological origin as CSK, that is cranial neural crest...
March 13, 2018: Journal of Cellular and Molecular Medicine
Aleksandra Klimczak, Urszula Kozlowska, Maciej Kurpisz
Muscular dystrophies represent a group of diseases which may develop in several forms, and severity of the disease is usually associated with gene mutations. In skeletal muscle regeneration and in muscular dystrophies, both innate and adaptive immune responses are involved. The regenerative potential of mesenchymal stem/stromal cells (MSCs) of bone marrow origin was confirmed by the ability to differentiate into diverse tissues and by their immunomodulatory and anti-inflammatory properties by secretion of a variety of growth factors and anti-inflammatory cytokines...
March 13, 2018: Archivum Immunologiae et Therapiae Experimentalis
Melissa Lo Monaco, Greet Merckx, Jessica Ratajczak, Pascal Gervois, Petra Hilkens, Peter Clegg, Annelies Bronckaers, Jean-Michel Vandeweerd, Ivo Lambrichts
Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs) or induced pluripotent stem cells (iPSCs) have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain uncertain. Stem cells can contribute to cartilage repair via chondrogenic differentiation, via immunomodulation, or by the production of paracrine factors and extracellular vesicles...
2018: Stem Cells International
Nevin Witman, Makoto Sahara
Major cardiovascular events including myocardial infarction (MI) continue to dominate morbidity rates in the developed world. Although multiple device therapies and various pharmacological agents have been shown to improve patient care and reduce mortality rates, clinicians and researchers alike still lack a true panacea to regenerate damaged cardiac tissue. Over the previous two to three decades, cardiovascular stem cell therapies have held great promise. Several stem cell-based approaches have now been shown to improve ventricular function and are documented in preclinical animal models as well as phase I and phase II clinical trials...
2018: Stem Cells International
Olena Pogozhykh, Volodymyr Prokopyuk, Constança Figueiredo, Denys Pogozhykh
Placental structures, capable to persist in a genetically foreign organism, are a natural model of allogeneic engraftment carrying a number of distinctive properties. In this review, the main features of the placenta and its derivatives such as structure, cellular composition, immunological and endocrine aspects, and the ability to invasion and deportation are discussed. These features are considered from a perspective that determines the placental material as a unique source for regenerative cell therapies and a lesson for immunological tolerance...
2018: Stem Cells International
Heiko Lemcke, Natalia Voronina, Gustav Steinhoff, Robert David
During the past decades, stem cell-based therapy has acquired a promising role in regenerative medicine. The application of novel cell therapeutics for the treatment of cardiovascular diseases could potentially achieve the ambitious aim of effective cardiac regeneration. Despite the highly positive results from preclinical studies, data from phase I/II clinical trials are inconsistent and the improvement of cardiac remodeling and heart performance was found to be quite limited. The major issues which cardiac stem cell therapy is facing include inefficient cell delivery to the site of injury, accompanied by low cell retention and weak effectiveness of remaining stem cells in tissue regeneration...
2018: Stem Cells International
Luís A Rocha, Rui A Sousa, David A Learmonth, António J Salgado
Spinal cord injury (SCI) represents an extremely debilitating condition for which no efficacious treatment is available. One of the main contributors to the inhospitable environment found in SCI is the vascular disruption that happens at the moment of injury that compromises the blood-spinal cord barrier (BSCB) and triggers a cascade of events that includes infiltration of inflammatory cells, ischemia and intraparenchymal hemorrhage. Due to the unsatisfactory nature of revascularization following SCI, restoring vascular perfusion and the BSCB seems an interesting way of modulating the lesion environment into a regenerative phenotype, with a potential increase in functional recovery...
2018: Frontiers in Pharmacology
Kristina Glenske, Phil Donkiewicz, Alexander Köwitsch, Nada Milosevic-Oljaca, Patrick Rider, Sven Rofall, Jörg Franke, Ole Jung, Ralf Smeets, Reinhard Schnettler, Sabine Wenisch, Mike Barbeck
The regeneration of bone tissue is the main purpose of most therapies in dental medicine. For bone regeneration, calcium phosphate (CaP)-based substitute materials based on natural (allo- and xenografts) and synthetic origins (alloplastic materials) are applied for guiding the regeneration processes. The optimal bone substitute has to act as a substrate for bone ingrowth into a defect, as well as resorb in the time frame needed for complete regeneration up to the condition of restitution ad integrum . In this context, the modes of action of CaP-based substitute materials have been frequently investigated, where it has been shown that such materials strongly influence regenerative processes such as osteoblast growth or differentiation and also osteoclastic resorption due to different physicochemical properties of the materials...
March 12, 2018: International Journal of Molecular Sciences
Przemysław Janas, Iwona Kucybała, Małgorzata Radoń-Pokracka, Hubert Huras
Telocytes are emerging cell population localized in the stroma of numerous organs, characterized by a distinctive morphology - small cell body with very long, slender prolongations, termed telopodes. Those cells can be found in the whole female reproductive system: in the vagina, uterus, oviducts and ovaries, mammary glands and also in the placenta. In our review, we aim at complete and transparent revision of the current knowledge of telocytes' localization and function, enriched by the analysis of the possible future direction of development of their clinical applications...
March 13, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Shin-Ichi Kanemaru, Rie Kanai, Misaki Yoshida, Yuji Kitada, Kaoru Omae, Shigeru Hirano
OBJECTIVE: To apply regenerative treatment for tympanic membrane (TM) perforation to patients with severe calcification of the TM, cholesteatomas, or tumors localized to the tympanic cavity. STUDY DESIGN: Controlled clinical pilot study. SETTING: General hospitals. PATIENTS: Forty-five patients (age: 8-85; M = 19, F = 26) were selected from patients with or without TM perforation for the regenerative treatment...
April 2018: Otology & Neurotology
Huihui Wang, Qi Zhong, Tianshu Yang, Ying Qi, Mengchen Fu, Xi Yang, Lu Qiao, Qi Ling, Shangfeng Liu, Yumei Zhao
Dental pulp stem cells (DPSCs) and stem cells from human exfoliated deciduous teeth (SHED) are types of human dental tissue‑derived mesenchymal stem cells (MSCs). These cells possess a capacity for self‑renewal, multilineage differentiation potential and immunomodulatory functions. Previous studies have reported that DPSCs and SHED may be beneficial in regenerative treatments and immunotherapy. The substantial expansion of cells in vitro is a prerequisite to obtaining adequate cell numbers required for cell‑based therapy...
March 9, 2018: Molecular Medicine Reports
Carlos A Aguilar, Sarah M Greising, Alain Watts, Stephen M Goldman, Chelsea Peragallo, Christina Zook, Jacqueline Larouche, Benjamin T Corona
Skeletal muscle possesses a remarkable capacity to regenerate when injured, but when confronted with major traumatic injury resulting in volumetric muscle loss (VML), the regenerative process consistently fails. The loss of muscle tissue and function from VML injury has prompted development of a suite of therapeutic approaches but these strategies have proceeded without a comprehensive understanding of the molecular landscape that drives the injury response. Herein, we administered a VML injury in an established rodent model and monitored the evolution of the healing phenomenology over multiple time points using muscle function testing, histology, and expression profiling by RNA sequencing...
December 2018: Cell Death Discovery
Mostafa Assem, Samia Kamal, Dina Sabry, Nadia Soliman, Riham M Aly
BACKGROUND: Stem cells have recently received great interest as potential therapeutics alternative for a variety of diseases. The oral and maxillofacial region, in particular, encompasses a variety of distinctive mesenchymal (MSC) populations and is characterized by a potent multilineage differentiation capacity. AIM: In this report, we aimed to investigate the effect of diabetes on the proliferation potential of stem cells isolated from controlled diabetic patients (type 2) and healthy individuals...
February 15, 2018: Open Access Macedonian Journal of Medical Sciences
L R Galieva, Y O Mukhamedshina, E R Akhmetzyanova, Z E Gilazieva, S S Arkhipova, E E Garanina, A A Rizvanov
Spinal cord injury (SCI) unavoidably results in death of not only neurons but also glial cells. In particular, the death of oligodendrocytes leads to impaired nerve impulse conduction in intact axons. However, after SCI, the Schwann cells (SCs) are capable of migrating towards an area of injury and participating in the formation of functional myelin. In addition to SCI, cell-based therapy can influence the migration of SCs and the expression of their molecular determinants. In a number of cases, it can be explained by the ability of implanted cells to secrete neurotrophic factors (NTFs)...
2018: Stem Cells International
Sucharita Boddu, Peter W Hashim, John K Nia, Rebecca Horowitz, Aaron Farberg, Gary Goldenberg
Stem cell therapies are at the forefront of regenerative aesthetic medicine. Multipotent stem cells and induced pluripotent stem cells (iPSCs), progenitor cells that result from the dedifferentiation of specialized adult cells, have demonstrated promise in tissue regeneration for a wide range of dermatologic conditions and aesthetic applications. Herein, we review the potential of stem cells as a new frontier in aesthetic dermatology.
January 2018: Cutis; Cutaneous Medicine for the Practitioner
Wen Yin, Xing Li, Yannan Zhao, Jun Tan, Shuyu Wu, Yudong Cao, Juan Li, Hecheng Zhu, Weidong Liu, Guihua Tang, Li Meng, Lei Wang, Bin Zhu, Gousiyi Wang, Meizuo Zhong, Xingdong Liu, Dan Xie, Bing Chen, Caiping Ren, Zhifeng Xiao, Xingjun Jiang, Jianwu Dai
Treatment of spinal cord injury (SCI) remains a clinical challenge worldwide because of the complicated inhibitory microenvironment formed post-injury, reduced axonal regenerative ability of spinal cord neurons, and scarcity of endogenous neurogenesis within the lesion center. Taxol, in addition to stabilizing microtubules, has shown potential for decreasing axonal degeneration and reducing scar formation after SCI in rodents. In this study, we further verified the therapeutic effects and clinical potential of Taxol on restriction of scar formation and promotion of neuronal regeneration and functional recovery after severe spinal cord transection in a large animal (canine) model...
March 12, 2018: Biomaterials Science
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