Author: Middleton, Ryan ; Zhang, Rui ; Grigorian Shamagian, Lilian ; Echavez, Antonio ; Rogers, Russell G ; Mariscal, Javier ; Marbán, Eduardo ; Liu, Weixin ; Fourier, Mario ; Sanchez, Liz ; Luther, Kristin ; Angert, David ; Jaghatspanyan, Eva ; Antes, Travis ; Valle, Jackelyn

Rejuvenation of an old organism was achieved in heterochronic parabiosis experiments, implicating different soluble factors in this effect. Extracellular vesicles (EVs) are the secretory effectors of many cells, including cardiosphere-derived cells (CDCs) with demonstrated anti-senescent effect. 1. To determine the role of EVs (versus other blood fractions) on the rejuvenating effect of the young blood. 2. To evaluate the anti-aging properties of therapeutically administered EVs secreted by young-CDCs in an old organism. Neonatal blood fractioned in 4 components (whole blood, serum, EV-depleted serum and purified EVs) was used to treat old human cardiac stromal cells (CSPCs). CDCs were generated from neonatal rat hearts and the secreted CDC-EVs were purified. CDC-EVs were then tested in naturally-aged rats, using monthly injections over 4-months period. For validation in human samples, pediatric CDC-EVs were tested in aged human CSPCs and progeric fibroblasts. While the purified EVs reproduced the rejuvenating effects of the whole blood, CSPCs treated with EV-depleted serum exhibited the highest degree of senescence. Treatment with young CDC-EVs induce structural and functional improvements in the heart, lungs, skeletal muscle, and kidneys of old rats, while favorably modulating glucose metabolism and anti-senescence pathways. Lifespan was prolonged. EVs secreted by young CDCs exert broad-ranging anti-aging effects in aged rodents and in cellular models of human senescence. Our work not only identifies CDC-EVs as possible therapeutic candidates for a wide range of age-related pathologies, but also raises the question of whether EVs function as endogenous modulators of senescence.

01 Nov 2020·Life SciencesQ3 · MEDICINE

Targeted doxorubicin-loaded mesenchymal stem cells-derived exosomes as a versatile platform for fighting against colorectal cancer

Q3 · MEDICINE

Article

Author: Bagheri, Elnaz ; Farzad, Sara Amel ; Alibolandi, Mona ; Ramezani, Mohammad ; Taghdisi, Seyed Mohammad ; Abnous, Khalil

Exosomes hold great potential for cancer treatment to deliver therapeutics due to its inherent low immunogenicity. Exosomes are biocompatible cell-exocytosed secreted vesicles by most cell types, which can be used to construct novel biomanufacturing platform for drug delivery and cancer therapy. In this study, we implemented nano-sized vesicles which were secreted by mesenchymal stem cell (MSC), to encapsulate doxorubicin (DOX) through electroporation method (DOX@exosome). DOX was loaded into exosomes, with an encapsulation efficiency of up to 35% and separated by ultracentrifugation. Subsequently, carboxylic acid-end MUC1 aptamer was used to covalently decorate the surface amine groups of the exosomes via amide bond formation to provide selective guided drug delivery (DOX@exosome-apt). The data showed that the DOX@exosome-apt provided highly efficient DOX transportation to MUC1-positive cancer cells in vitro as confirmed by MTT and flow cytometry experiments. Moreover, in vivo study on ectopic model of C26 (mouse colon adenocarcinoma) in BALB/c mice indicated that the single dose intravenous injection of DOX@exosome-apt significantly suppress tumor growth in comparison with free DOX. Ex vivo fluorescent imaging also verified the desirable biodistribution of DOX@exosome-apt by exhibiting higher tumor accumulation and faster liver clearance in comparison with DOX@exosome and free DOX. It could be concluded that MUC1 aptamer-decorated exosomes can be implemented therapeutically for the safe and versatile delivery of DOX to colon adenocarcinoma, thus offering valuable platform for clinical applications.

01 Aug 2020·Arthroscopy: The Journal of Arthroscopic & Related SurgeryQ1 · MEDICINE

Intra-Articular Injections of Mesenchymal Stem Cell Exosomes and Hyaluronic Acid Improve Structural and Mechanical Properties of Repaired Cartilage in a Rabbit Model

Q1 · MEDICINE

Article

Author: Wong, Keng Lin ; Lai, Ruenn Chai ; Wang, Ming ; Lim, Sai Kiang ; Toh, Wei Seong ; Lee, Eng Hin ; Zhang, Shipin ; Ren, Xiafei ; Afizah, Hassan ; Hui, James Hoi Po

PURPOSETo compare the efficacy of mesenchymal stem cell (MSC) exosomes with hyaluronic acid (HA) against HA alone for functional cartilage regeneration in a rabbit osteochondral defect model.METHODSCritical-size osteochondral defects (4.5-mm diameter and 1.5-mm depth) were created on the trochlear grooves in the knees of 18 rabbits and were randomly allocated to 2 treatment groups: (1) exosomes and HA combination and (2) HA alone. Three 1-mL injections of either exosomes and HA or HA alone were administered intra-articularly immediately after surgery and thereafter at 7 and 14 days after surgery. At 6 and 12 weeks, gross evaluation, histologic and immunohistochemical analysis, and scoring were performed. The functional biomechanical competence of the repaired cartilage also was evaluated.RESULTSCompared with defects treated with HA, defects treated with exosomes and HA showed significant improvements in macroscopic scores (P = .032; P = .001) and histologic scores (P = .005; P < .001) at 6 and 12 weeks, respectively. Defects treated with exosomes and HA also demonstrated improvements in mechanical properties compared with HA-treated defects, with significantly greater Young's moduli (P < .05) and stiffness (P < .05) at 6 and 12 weeks. By 12 weeks, the newly-repaired tissues in defects treated with exosomes and HA composed mainly of hyaline cartilage that are mechanically and structurally superior to that of HA-treated defects and demonstrated mechanical properties that approximated that of adjacent native cartilage (P > .05). In contrast, HA-treated defects showed some repair at 6 weeks, but this was not sustained, as evidenced by significant deterioration of histologic scores (P = .002) and a plateau in mechanical properties from 6 to 12 weeks.CONCLUSIONSThis study shows that the combination of MSC exosomes and HA administered at a clinically acceptable frequency of 3 intra-articular injections can promote sustained and functional cartilage repair in a rabbit post-traumatic cartilage defect model, when compared with HA alone.CLINICAL RELEVANCEHuman MSC exosomes and HA administered in combination promote functional cartilage repair and may represent a promising cell-free therapy for cartilage repair in patients.

100 Deals associated with Engineered exosomes (Capricor Therapeutics)

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Indication	Highest Phase	Country/Location	Organization	Date
Cerebral Hemorrhage	Preclinical	US	Capricor Therapeutics, Inc.	-
Cerebral Hemorrhage	Preclinical	US	US Army Institute of Surgical Research	-
Shock, Hemorrhagic	Preclinical	US	Capricor Therapeutics, Inc.	-
Shock, Hemorrhagic	Preclinical	US	US Army Institute of Surgical Research	-

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