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Regenerative injection therapy

John P Leach, James F Martin
PURPOSE OF REVIEW: Current pharmacologic treatments for cardiovascular disease do not correct the underlying cellular defect, the loss of cardiomyocytes. With recent advancements in cardiac regenerative approaches, the induction of endogenous mature cardiomyocyte proliferation has emerged as a new possibility. Here, we review progress made toward the regeneration of cardiac tissue in the mammalian heart through the stimulation of mature cardiomyocyte renewal. RECENT FINDINGS: The targeting of several developmental and signaling pathways has been shown to stimulate cell cycle re-entry in mature cardiomyocytes...
June 14, 2018: Current Cardiology Reports
Stuart Young, Lauren Elizabeth Flynn, Brian G Amsden
Injectable hydrogels have the potential to enhance stem cell-based therapies by improving cell localization, retention, and survival following transplantation. The inflammatory response to both the hydrogel and the encapsulated cells is a critical aspect of this strategy, with macrophages being highly involved in the process of hydrogel remodelling, angiogenesis, and tissue regeneration. As a step towards the development of a cell-based strategy for therapeutic angiogenesis, the current work compared the intramuscular injection of allogeneic rat adipose-derived stem/stromal cells (rASCs) in an in situ-gelling hydrogel to the injection of the hydrogel alone and rASCs in saline in an immunocompetent rat model by immunohistochemical analysis over 4 weeks...
June 8, 2018: Tissue Engineering. Part A
Pedro M D Moreno, Ana R Ferreira, Daniela Salvador, Maria T Rodrigues, Marília Torrado, Eva D Carvalho, Ulf Tedebark, Mónica M Sousa, Isabel F Amaral, Jesper Wengel, Ana P Pêgo
After spinal cord injury (SCI), nerve regeneration is severely hampered due to the establishment of a highly inhibitory microenvironment at the injury site, through the contribution of multiple factors. The potential of antisense oligonucleotides (AONs) to modify gene expression at different levels, allowing the regulation of cell survival and cell function, together with the availability of chemically modified nucleic acids with favorable biopharmaceutical properties, make AONs an attractive tool for novel SCI therapy developments...
June 1, 2018: Molecular Therapy. Nucleic Acids
Qian Xu, A Sigen, Yongsheng Gao, Linru Guo, Jack Creagh-Flynn, Dezhong Zhou, Udo Greiser, Yixiao Dong, Fagang Wang, Hongyun Tai, Wenguang Liu, Wei Wang, Wenxin Wang
The injectable hydrogel with desirable biocompatibility and tunable properties can improve the efficacy of stem cell-based therapy. However, the development of injectable hydrogel remains a great challenge due to the restriction of crosslinking efficiency, mechanical properties, and potential toxicity. Here, we report that a new injectable hydrogel system were fabricated from hyperbranched multi-acrylated poly(ethylene glycol) macromers (HP-PEGs) and thiolated hyaluronic acid (HA-SH) and used as a stem cell delivery and retention platform...
May 24, 2018: Acta Biomaterialia
Philippe Hernigou, Gilles Guerin, Yasuhiro Homma, Arnaud Dubory, Nathalie Chevallier, Hélène Rouard, Charles Henri Flouzat Lachaniette
PURPOSE: Despite multiple possible treatments, the risk of collapse remains the main problem of osteonecrosis. Heart failure (HF). In an effort to address the reverse this issue, curative strategies with regenerative medicine are increasingly being considered. The aim of this technology is to halt or reverse progression of the disease to collapse. MATERIAL AND METHODS: The pioneering report by Hernigou published in 2002 was the first pilot study suggesting that injection of bone marrow stem cells was a safe approach able to improve osteonecrosis in patients with early stages...
May 24, 2018: International Orthopaedics
Marieke Barnhoorn, Eveline de Jonge-Muller, Ilse Molendijk, Mandy van Gulijk, Oscar Lebbink, Stef Janson, Mark Schoonderwoerd, Danny van der Helm, Andrea van der Meulen-de Jong, Lukas Hawinkels, Hein Verspaget
Background: Mesenchymal stromal cells (MSCs) are a potential therapeutic modality in inflammatory bowel diseases (IBDs) because of their immunomodulatory and regenerative properties. However, when injected systemically, only a small portion of the cells, if any, reach the inflamed colon. In this study, we assessed whether endoscopic injections of MSCs into the intestinal wall of the inflamed colon affect the course of experimental colitis. Furthermore, we investigated if injection of aggregated MSCs in spheroids could enhance their therapeutic ability...
May 22, 2018: Inflammatory Bowel Diseases
Yaqi Yin, Haojie Hao, Yu Cheng, Jieqing Gao, Jiejie Liu, Zongyan Xie, Qi Zhang, Li Zang, Weidong Han, Yiming Mu
Umbilical cord-derived mesenchymal stem cells (UC-MSCs), with both immunomodulatory and pro-regenerative properties, are promising for the treatment of type 2 diabetes mellitus (T2DM). As efficient cell therapy largely relies on appropriate homing to target tissues, knowing where and to what extent injected UC-MSCs have homed is critically important. However, bio-distribution data for UC-MSCs in T2DM subjects are extremely limited. Beneficial effects of UC-MSCs on T2DM subjects are associated with increased M2 macrophages, but no systemic evaluation of M2 macrophages has been performed in T2DM individuals...
May 15, 2018: International Immunopharmacology
Katrien Neyrinck, Natacha Breuls, Bryan Holvoet, Wouter Oosterlinck, Esther Wolfs, Hubert Vanbilloen, Olivier Gheysens, Robin Duelen, Willy Gsell, Ivo Lambrichts, Uwe Himmelreich, Catherine M Verfaillie, Maurilio Sampaolesi, Christophe M Deroose
Rationale: Pluripotent stem cells (PSCs) are being investigated as a cell source for regenerative medicine since they provide an infinitive pool of cells that are able to differentiate towards every cell type of the body. One possible therapeutic application involves the use of these cells to treat myocardial infarction (MI), a condition where billions of cardiomyocytes (CMs) are lost. Although several protocols have been developed to differentiate PSCs towards CMs, none of these provide a completely pure population, thereby still posing a risk for neoplastic teratoma formation...
2018: Theranostics
Vivian W Lau, Simon R Platt, Harrison E Grace, Emily W Baker, Franklin D West
Introduction: Stroke is the leading cause of disability in the United States but current therapies are limited with no regenerative potential. Previous translational failures have highlighted the need for large animal models of ischemic stroke and for improved assessments of functional outcomes. The aims of this study were first, to create a post-stroke functional outcome assessment scale in a porcine model of middle cerebral artery occlusion (MCAO) and second, to use this scale to determine the effect of human-induced-pluripotent-cell-derived neural progenitor cells (iNPCs) on functional outcome in this large animal stroke model...
May 2018: Brain and Behavior
José M Lasso, Daniel Poletti, Batolomé Scola, Pedro Gómez-Vilda, Ana I García-Martín, María Eugenia Fernández-Santos
Background: Paralysis of one vocal fold leads to glottal gap and vocal fold insufficiency that has significant impact upon a patient's quality of life. Fillers have been tested to perform intracordal injections, but they do not provide perdurable results. Early data suggest that enriching fat grafts with adipose-derived regenerative cells (ADRCs) promote angiogenesis and modulate the immune response, improving graft survival. The aim of this study is to propose ADRC-enriched adipose tissue grafts as effective filler for the paralyzed vocal fold to use it for functional reconstruction of the glottal gap...
2018: Stem Cells International
Se-Joon Oh, Hee-Young Park, Kyung-Un Choi, Sung-Won Choi, Sung-Dong Kim, Soo-Keun Kong, Kyu-Sup Cho
Tissue engineering cell-based therapy using induced pluripotent stem cells and adipose-derived stem cells (ASCs) may be promising tools for therapeutic applications in tissue engineering because of their abundance, relatively easy harvesting, and high proliferation potential. The purpose of this study was to investigate whether ASCs can promote the auricular cartilage regeneration in the rabbit. In order to assess their differentiation ability, ASCs were injected into the midportion of a surgically created auricular cartilage defect in the rabbit...
2018: Mediators of Inflammation
Sadegh Davoudi, Chih-Ying Chin, Michael J Cooke, Roger Y Tam, Molly S Shoichet, Penney M Gilbert
Adult skeletal muscle tissue harbors the capacity for self-repair due to the presence of tissue resident muscle stem cells (MuSCs). Advances in the area of prospective MuSC isolation demonstrated the potential of cell transplantation therapy as a regenerative medicine strategy to restore strength and long-term regenerative capacity to aged, injured, or diseased skeletal muscle tissue. However, cell loss during ejection, limits to post-injection proliferation, and poor donor cell dispersion distal to the injection site are amongst hurdles to overcome to maximize MuSC transplant impact...
April 26, 2018: Biomaterials
Katrin Wacker, Keith H Baratz, Michael P Fautsch, Sanjay V Patel
Unraveling the genetic mechanisms of Fuchs endothelial corneal dystrophy has opened new possibilities for future targeted medical therapy of the disease. Until these possibilities mature, regenerative semi-surgical approaches by cell injection or cell sheet transfer could help expand the donor pool, and possibly enable autologous transplantation. Descemet membrane stripping alone and acellular Descemet membrane transfer are more immediate surgical approaches that could be temporary treatments in some patients, though there is a lack of understanding of the factors that predict success for these procedures...
May 3, 2018: Klinische Monatsblätter Für Augenheilkunde
Robin M Heider, John A Smestad, Hernan Nicolas Lemus, Brandon Wilbanks, Arthur E Warrington, Justin P Peters, Moses Rodriguez, L James Maher
Multiple sclerosis (MS) is a debilitating disease for which regenerative therapies are sought. We have previously described human antibodies and DNA aptamer-streptavidin conjugates that promote remyelination after systemic injection into mice infected by Theiler's murine encephalomyelitis virus. Here, we report an in vitro assay of myelin binding with results that correlate with remyelination outcome in vivo , as shown for data from a set of DNA aptamer complexes of different size and formulation. This in vitro assay will be valuable for future screening of MS regenerative therapies targeting remyelination...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
Gun-Il Im
Osteoarthritis (OA) is the most common form of arthritis. Over the last 20 years, attempts have been made to regenerate articular cartilage to overcome the limitations of conventional treatments. As OA is generally associated with larger and diffuse involvement of articular surfaces and alteration of joint homeostasis, a tissue engineering approach for cartilage regeneration is more difficult than in simple chondral defects. Autologous and allogeneic mesenchymal stem cells (MSCs) have rapidly emerged as investigational products for cartilage regeneration...
June 2018: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
Mark G MacAskill, Jaimy Saif, Alison Condie, Maurits A Jansen, Thomas J MacGillivray, Adriana A S Tavares, Lucija Fleisinger, Helen L Spencer, Marie Besnier, Ernesto Martin, Giovanni Biglino, David E Newby, Patrick W F Hadoke, Joanne C Mountford, Costanza Emanueli, Andrew H Baker
Pluripotent stem cell-derived differentiated endothelial cells offer high potential in regenerative medicine in the cardiovascular system. With the aim of translating the use of a human stem cell-derived endothelial cell product (hESC-ECP) for treatment of critical limb ischemia (CLI) in man, we report a good manufacturing practice (GMP)-compatible protocol and detailed cell tracking and efficacy data in multiple preclinical models. The clinical-grade cell line RC11 was used to generate hESC-ECP, which was identified as mostly endothelial (60% CD31+ /CD144+ ), with the remainder of the subset expressing various pericyte/mesenchymal stem cell markers...
March 28, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Fernando de la Portilla, Yaiza Yuste, Sheila Pereira, Carolina Olano, Maria Victoria Maestre, Francisco Javier Padillo
Background: Multipotent mesenchymal stem cells (MSCs) have been used in inflammatory bowel diseases because of their immunomodulatory and regenerative properties. We investigated their local use in an experimental model of colitis in the rat. Materials and Methods: Colitis was induced into 20 Wistar rats with local TNBS instillation. Allogeneic stem cells were derived from rat adipose tissue and labeled with PKH2 linker dye with creation of a control and a second group treated by a local injection into the rectal wall of 2×10⁶ allogeneic adipose tissue-derived stem cells (ADSCs)...
May 30, 2018: International Journal of Stem Cells
Vinicius Tieppo Francio, Robert S Dima, Chris Towery, Saeid Davani
Regenerative injection therapy and low level laser therapy are alternative remedies known for their success in the treatment and symptomatic management of chronic musculoskeletal conditions. In response to the growing demand for alternative therapies in the face of the opioid epidemic, the authors conduct a literature review to investigate the potential for prolotherapy and LLLT to be used adjunctively to manage chronic osteoarthritis (OA). OA is a degenerative chronic musculoskeletal condition on the rise in North America, and is frequently treated with opioid medications...
October 2017: Anesthesiology and Pain Medicine
Chelsea R Wood, Ibtesam R T Al Delfi, John F Innes, Peter Myint, William E B Johnson
The multifactorial complexity of spinal cord injuries includes the formation of a glial scar, of which chondroitin sulphated proteoglycans (CSPG) are an integral component. Previous studies have shown CSPG to have inhibitory effects on endothelial and neuronal cell growth, highlighting the difficulty of spinal cord regeneration. Mesenchymal stem/stromal cells (MSC) are widely used as a cell therapy, and there is mounting evidence for their angiogenic and neurotrophic paracrine properties. However, in vivo studies have observed poor engraftment and survival of MSC when injected into SCI...
April 19, 2018: Biochimie
Saeed Zahiri, Elahe Masaeli, Elahe Poorazizi, Mohammad Hossein Nasr-Esfahani
Current studies based on regenerative medicine suggest, decellularized extracellular matrix (DC-ECM) components can regulate cell phenotype. In this regard, it is believed, presence of cartilage extracellular matrix particles in culture condition could produce physical and biochemical supportive cues for chondrogenesis. In this study, DC-ECM nanoparticles with average size of 61.5± 22.4 nm were produced by decellularization and mechanical processing. Homogenous distribution and nano scale size of yield particles were observed by Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) microscopy imaging...
April 17, 2018: Journal of Biomedical Materials Research. Part A
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