Cell Therapy: Types, Regulation, and Clinical Benefits

Osteoarthritis (OA) has generally been introduced as a degenerative disease; however, it has recently been understood as a low-grade chronic inflammatory process that could promote symptoms and accelerate the progression of OA. Current treatment strategies, including corticosteroid injections, have no impact on the OA disease progression. Mesenchymal stem cells (MSCs) based therapy seem to be in the spotlight as a disease-modifying treatment because this strategy provides enlarged anti-inflammatory and chondroprotective effects. Currently, bone marrow, adipose derived, synovium-derived, and Wharton’s jelly-derived MSCs are the most widely used types of MSCs in the cartilage engineering. MSCs exert immunomodulatory, immunosuppressive, antiapoptotic, and chondrogenic effects mainly by paracrine effect. Because MSCs disappear from the tissue quickly after administration, recently, MSCs-derived exosomes received the focus for the next-generation treatment strategy for OA. MSCs-derived exosomes contain a variety of miRNAs. Exosomal miRNAs have a critical role in cartilage regeneration by immunomodulatory function such as promoting chondrocyte proliferation, matrix secretion, and subsiding inflammation. In the future, a personalized exosome can be packaged with ideal miRNA and proteins for chondrogenesis by enriching techniques. In addition, the target specific exosomes could be a gamechanger for OA. However, we should consider the off-target side effects due to multiple gene targets of miRNA.

/pdf/state-of-the-art-the-immunomodulatory-role-of-mscs-for-1eb48kpk.pdf

State of the Art: The Immunomodulatory Role of MSCs for Osteoarthritis

The recent rapid development in the field of extracellular vesicles (EVs) based nanotechnology has provided unprecedented opportunities for nanomedicine platforms. As natural nanocarriers, EVs such as exosomes, exosome-like nanoparticles and outer membrane vesicles (OMVs), have unique structure/composition/morphology characteristics, and show excellent physical and chemical/biochemical properties, making them a new generation of theranostic nanomedicine. Here, we reviewed the characteristics of EVs from the perspective of their formation and biological function in inflammatory bowel disease (IBD). Moreover, EVs can crucially participate in the interaction and communication of intestinal epithelial cells (IECs)-immune cells-gut microbiota to regulate immune response, intestinal inflammation and intestinal homeostasis. Interestingly, based on current representative examples in the field of exosomes and exosome-like nanoparticles for IBD treatment, it is shown that plant, milk, and cells-derived exosomes and exosome-like nanoparticles can exert a therapeutic effect through their components, such as proteins, nucleic acid, and lipids. Moreover, several drug loading methods and target modification of exosomes are used to improve their therapeutic capability. We also discussed the application of exosomes and exosome-like nanoparticles in the treatment of IBD. In this review, we aim to better and more clearly clarify the underlying mechanisms of the EVs in the pathogenesis of IBD, and provide directions of exosomes and exosome-like nanoparticles mediated for IBD treatment. 

Extracellular Vesicles: The Next Generation Theranostic Nanomedicine for Inflammatory Bowel Disease

Mesenchymal stem cell-derived exosomes have been under investigation as potential treatments for a diverse range of diseases, and many animal and clinical trials have achieved encouraging results. However, it is well known that the biological activity of the exosomes is key to their therapeutic properties; however, till date, it has not been completely understood. Previous studies have provided different explanations of therapeutic mechanisms of the exosomes, including anti-inflammatory, immunomodulatory, and anti-aging mechanisms. The pathological effects of oxidative stress often include organ damage, inflammation, and disorders of material and energy metabolism. The evidence gathered from research involving animal models indicates that exosomes have antioxidant properties, which can also explain their anti-inflammatory and cytoprotective effects. In this study, we have summarized the antioxidant effects of exosomes in in vivo and in vitro models, and have evaluated the anti-oxidant mechanisms of exosomes by demonstrating a direct reduction in excessive reactive oxygen species (ROS), promotion of intracellular defence of anti-oxidative stress, immunomodulation by inhibiting excess ROS, and alteration of mitochondrial performance. Exosomes exert their cytoprotective and anti-inflammatory properties by regulating the redox environment and oxidative stress, which explains the therapeutic effects of exosomes in a variety of diseases, mechanisms that can be well preserved among different species.

Emerging Antioxidant Paradigm of Mesenchymal Stem Cell-Derived Exosome Therapy

Abstract The recent rapid development in the field of extracellular vesicles (EVs) based nanotechnology has provided unprecedented opportunities for nanomedicine platforms. As natural nanocarriers, EVs such as exosomes, exosome-like nanoparticles and outer membrane vesicles (OMVs), have unique structure/composition/morphology characteristics, and show excellent physical and chemical/biochemical properties, making them a new generation of theranostic nanomedicine. Here, we reviewed the characteristics of EVs from the perspective of their formation and biological function in inflammatory bowel disease (IBD). Moreover, EVs can crucially participate in the interaction and communication of intestinal epithelial cells (IECs)-immune cells-gut microbiota to regulate immune response, intestinal inflammation and intestinal homeostasis. Interestingly, based on current representative examples in the field of exosomes and exosome-like nanoparticles for IBD treatment, it is shown that plant, milk, and cells-derived exosomes and exosome-like nanoparticles can exert a therapeutic effect through their components, such as proteins, nucleic acid, and lipids. Moreover, several drug loading methods and target modification of exosomes are used to improve their therapeutic capability. We also discussed the application of exosomes and exosome-like nanoparticles in the treatment of IBD. In this review, we aim to better and more clearly clarify the underlying mechanisms of the EVs in the pathogenesis of IBD, and provide directions of exosomes and exosome-like nanoparticles mediated for IBD treatment.

https://www.dovepress.com/getfile.php?fileID=83642

https://journals.sagepub.com/doi/pdf/10.1177/0963689720943581

Comparison of Bone Marrow Aspirate Concentrate and Allogenic Human Umbilical Cord Blood Derived Mesenchymal Stem Cell Implantation on Chondral Defect of Knee: Assessment of Clinical and Magnetic Resonance Imaging Outcomes at 2-Year Follow-Up:

Studies regarding the development of metallosis following open reduction and internal fixation (ORIF) of fractures are rarely found in orthopedic literature. The aim of the current study was to assess metallosis following ORIF using distal fibular locking plates to treat distal fibular fractures. 69 patients who underwent surgery using locking compression plates to treat lateral malleolar fractures, with a minimum 1-year follow-up period and subsequent hardware removal were enrolled in our study. We divided the patients into 2 groups, to compare the complications and demographics: 38 patients, treated with ZPLP plate; 31 patients, treated with other plates. During 1 year of postoperative follow-up, 20 complications developed: 6 superficial infections at the operative site, 1 case of nonunion, 3 cases of osteitis, 4 cases of hypaesthesia, 2 cases of peripheral neuropathy, and 4 cases of metallosis. No statistical difference was found in the rate of complications when comparing the treatment groups (Mann–Whitney U test, p < .05) except for metallosis. All 4 patients who developed metallosis were treated using a ZPLP plate, and metallosis did not develop at all in patients who underwent surgery using other plates. In our study, metallosis developed more than was previously known, particularly after using LCPs to treat lateral malleolar fractures. Our findings and those in recent publications support the possibility that metallosis can occur not only in patients with arthroplasties, but also in patients with open reduction and internal fixation with LCPs. Surgeons should be aware of such risk of metallosis and be careful to select proper plates for internal fixation.

Metallosis after using distal fibular locking plate for lateral malleolar fractures: a retrospective study.

Introduction:In this study, we evaluated how muscle mass and bone density affect postoperative functional scores and subsequent fracture rates and investigated the correlation between sarcopenia an...

https://journals.sagepub.com/doi/pdf/10.1177/2151459320940568

Effect of Osteosarcopenia on Postoperative Functional Outcomes and Subsequent Fracture in Elderly Hip Fracture Patients.

Background: With the development of health care–related mobile apps, attempts have been made to implement remote patient-reported outcome measures (PROMs). In order for remote PROMs to be widely used by mobile apps, the results should not be different depending on the location; that is, remote PROM results performed in locations other than hospitals should be able to obtain reliable results equivalent to those performed in hospitals, and this is very important. However, to our knowledge, there are no studies that have assessed the reliability of PROMs using mobile apps according to the location by comparing the results performed remotely from the hospital and performed at the outpatient visits.
Objective: The purpose of this study was to evaluate the reliability of remote PROMs using mobile apps compared to PROMs performed during outpatient follow-up visits after arthroscopic shoulder surgery.
Methods: A total of 174 patients who underwent arthroscopic rotator cuff repair completed questionnaires 2 days before visiting the clinic for the 1-, 2-, 3-, 6-, and 12-month follow-ups (test A). The patients completed the questionnaires at the clinic (test B) using the same mobile app and device for the 1-, 2-, 3-, 6-, and 12-month follow-ups. Test-retest comparisons were performed to analyze the differences and reliability of the PROMs according to the period.
Results: Comparisons of tests A and B showed statistically significant differences at 1, 2, and 3 months (all Ps .05). The intraclass correlation values between the two groups were relatively low at the 1-, 2-, and 3-month follow-ups but were within the reliable range at 6 and 12 months after surgery. The rate of completion of tests A and B using the mobile app was significantly lower in the group older than 70 years than in the other groups for all postoperative periods (P<.001).
Conclusions: PROMs using mobile apps with different locations differed soon after surgery but were reliably similar after 6 months. The remote PROMs using mobile apps could be used reliably for the patient more than 6 months after surgery. However, it is to be expected that the use of mobile app–based questionnaires is not as useful in the group older than 70 years as in other age groups.

/pdf/the-reliability-of-remote-patient-reported-outcome-measures-21v1b3ya4r.pdf

The Reliability of Remote Patient-Reported Outcome Measures via Mobile Apps to Replace Outpatient Visits After Rotator Cuff Repair Surgery: Repetitive Test-Retest Comparison Study for 1-Year Follow-up.

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Papers

Comparison of Bone Marrow Aspirate Concentrate and Allogenic Human Umbilical Cord Blood Derived Mesenchymal Stem Cell Implantation on Chondral Defect of Knee: Assessment of Clinical and Magnetic Resonance Imaging Outcomes at 2-Year Follow-Up:

Metallosis after using distal fibular locking plate for lateral malleolar fractures: a retrospective study.

Effect of Osteosarcopenia on Postoperative Functional Outcomes and Subsequent Fracture in Elderly Hip Fracture Patients.

The Reliability of Remote Patient-Reported Outcome Measures via Mobile Apps to Replace Outpatient Visits After Rotator Cuff Repair Surgery: Repetitive Test-Retest Comparison Study for 1-Year Follow-up.