Comparative effectiveness of adipose-derived mesenchymal stromal cells in the management of knee osteoarthritis:A meta-analysis

BACKGROUND Osteoarthritis(OA)is the most common joint disorder,is associated with an increasing socioeconomic impact owing to the ageing population.AIM To analyze and compare the efficacy and safety of bone-marrow-derived mesenchymal stromal cells(BM-MSCs)and adipose tissue-derived MSCs(AD-MSCs)in knee OA management from published randomized controlled trials(RCTs).METHODS Independent and duplicate electronic database searches were performed,including PubMed,EMBASE,Web of Science,and Cochrane Library,until August 2021 for RCTs that analyzed the efficacy and safety of AD-MSCs and BM-MSCs in the management of knee OA.The visual analog scale(VAS)score for pain,Western Ontario McMaster Universities Osteoarthritis Index(WOMAC),Lysholm score,Tegner score,magnetic resonance observation of cartilage repair tissue score,knee osteoarthritis outcome score(KOOS),and adverse events were analyzed.Analysis was performed on the R-platform using OpenMeta(Analyst)software.Twenty-one studies,involving 936 patients,were included.Only one study compared the two MSC sources without patient randomization;hence,the results of all included studies from both sources were pooled,and a comparative critical analysis was performed.RESULTS At six months,both AD-MSCs and BM-MSCs showed significant VAS improvement(P=0.015,P=0.012);this was inconsistent at 1 year for BM-MSCs(P<0.001,P=0.539),and AD-MSCs outperformed BM-MSCs compared to controls in measures such as WOMAC(P<0.001,P=0.541),Lysholm scores(P=0.006;P=0.933),and KOOS(P=0.002;P=0.012).BM-MSC-related procedures caused significant adverse events(P=0.003)compared to AD-MSCs(P=0.673).CONCLUSION Adipose tissue is superior to bone marrow because of its safety and consistent efficacy in improving pain and functional outcomes.Future trials are urgently warranted to validate our findings and reach a consensus on the ideal source of MSCs for managing knee OA.

Is mandible derived mesenchymal stromal cells superior in proliferation and regeneration to long bone-derived mesenchymal stromal cells?

Mesenchymal stromal cells(MSCs)are cells with the characteristic ability of self-renewal along with the ability to exhibit multilineage differentiation.Bone marrow(BM)is the first tissue in which MSCs were identified and BM-MSCs are most commonly used among various MSCs in clinical settings.MSCs can stimulate and promote osseous regeneration.Due to the difference in the development of long bones and craniofacial bones,the mandibular-derived MSCs(M-MSCs)have distinct differentiation characteristics as compared to that of long bones.Both mandibular and long bone-derived MSCs are positive for MSC-associated markers such as CD-73,-105,and-106,stage-specific embryonic antigen 4 and Octamer-4,and negative for hematopoietic markers such as CD-14.

Machine learning and deep neural network-based learning in osteoarthritis knee

Osteoarthritis(OA)of the knee joint is considered the commonest musculoskeletal condition leading to marked disability for patients residing in various regions around the globe.Application of machine learning(ML)in doing research regarding OA has brought about various clinical advances viz,OA being diagnosed at preliminary stages,prediction of chances of development of OA among the population,discovering various phenotypes of OA,calculating the severity in OA structure and also discovering people with slow and fast progression of disease pathology,etc.Various publications are available regarding machine learning methods for the early detection of osteoarthritis.The key features are detected by morphology,molecular architecture,and electrical and mechanical functions.In addition,this particular technique was utilized to assess non-interfering,non-ionizing,and in-vivo techniques using magnetic resonance imaging.ML is being utilized in OA,chiefly with the formulation of large cohorts viz,the OA Initiative,a cohort observational study,the Multicentre Osteoarthritis Study,an observational,prospective longitudinal study and the Cohort Hip&Cohort Knee,an observational cohort prospective study of both hip and knee OA.Though ML has various contributions and enhancing applications,it remains an imminent field with high potential,also with its limitations.Many more studies are to be carried out to find more about the link between machine learning and knee osteoarthritis,which would help in the improvement of making decisions clinically,and expedite the necessary interventions.

Mesenchymal Stem Cells (MSCs) as a Novel Therapeutic Option for nCOVID-19—A Review

The novel Coronavirus Disease (nCOVID-19) is a highly contagious viral infection which emerged as “Pneumonia of Unknown Etiology” at Hubei province of Wuhan city in China. The health authorities provided a considerable empirical evidence after this outbreak and it was notified that the causative virus, named Novel Coronavirus (subsequently SARS-CoV-2) is the culprit for progressively exerting grim effects not only on individual patients but also on the International public health, with high mutational tendencies. WHO declared nCOVID-19 as a Pandemic on 11th March 2020. The spike glycoprotein of SARS-CoV-2 plays a pivotal role in the entry of virus into the cell and it further interacts with ACE-II receptors which are widely distributed on the human cell surface especially on alveolar type II cells (AT-2) and endothelium. The mortality in nCOVID-19 patients is usually preceded by acute respiratory distress syndrome (ARDS) because of the cytokine storm. Advanced molecular biology and regenerative sciences renders a breakthrough in the treatment of severely ill nCOVID-19 patients with Mesenchymal Stem Cells (MSCs). Autologous or allogenic MSCs attenuate cytokine storm, improvise lung compliance, regulate inflammatory response, maintain functional alveoli microenvironment, promote endogenous regeneration and repair with no or minimal side effects. MSCs are naturally resistant to this novel Coronavirus. Even though it is corroborated with evidences from current clinical trials and pilot study, we emphasize the need for conducting more clinical trials with ethical consideration to prove the efficacy and safety of MSCs in combating nCOVID-19 infection and its complications.

Evidence analysis on the utilization of platelet-rich plasma as an adjuvant in the repair of rotator cuff tears

BACKGROUND Platelet-rich plasma has been gaining popularity as an agent for biological augmentation either as the sole treatment modality or as an adjunct to surgical repair.There is substantial discrepancy in the results of the published meta-analyses;and the true efficacy and role of using autologous platelet-rich plasma(PRP)at the time of rotator cuff repair is still ambiguous.AIM To performed this systematic overview on the overlapping meta-analyses that analyzed autologous PRP as an adjuvant in the repair of rotator cuff tears and identify the studies which provide the current best evidence on this subject and generate recommendations for the same.METHODS We conducted independent and duplicate electronic database searches in PubMed,Web of Science,Scopus,Embase,Cochrane Database of Systematic Reviews,Reference Citation Analysis and the Database of Abstracts of Reviews of Effects on September 8,2021 to identify meta-analyses that analyzed the efficacy of PRP as an adjuvant in the repair of rotator cuff tears.Methodological quality assessment was made using Oxford Levels of Evidence,AMSTAR scoring and AMSTAR 2 grades.We then utilized the Jadad decision algorithm to identify the study with the highest quality to represent the current best evidence to generate the recommendation.RESULTS Twenty meta-analyses fulfilling the eligibility criteria were included.The AMSTAR scores of the included studies varied from 6-10(mean:7.9).All the included studies had critically low reliability in their summary of results due to their methodological flaws according to AMSTAR 2 grades.Significant heterogeneity was observed in the reporting of VAS,function outcome scores(longterm UCLA score,ASES score,SST score),operative time and long-term re-tear rates.Recent metaanalyses are more supportive of the role of intra-operative administration of PRPs at the bonetendon interface in improving the overall healing and re-tear rates,functional outcome and pain.The initial size of the tear and type of repair performed do not seem to affect the benefit of PRPs.Among the different preparations used,leucocyte poor(LP)-PRP possibly offers the greatest benefit as a biological augment in these situations.CONCLUSION Based on this systematic overview,we give a level II recommendation that intra-operative use of PRPs at the bone-tendon interface can augment the healing rate,reduce re-tears,enhance functional outcome and mitigate pain in patients undergoing arthroscopic rotator cuff repair.LPPRP possibly offers the greatest benefit in terms of healing rates,as compared with other platelet preparations.

Is cellular therapy beneficial in management of rotator cuff tears?Meta-analysis of comparative clinical studies

BACKGROUND Mesenchymal stromal cell(MSC)-based cellular therapy promotes type I collagen production,enhance mechanical strength of tissues,and enhance biology at the bone-tendon interface,which primarily explains their potential clinical utility in rotator cuff(RC)tears.AIM To analyze the efficacy and safety of cellular therapy utilizing MSCs in the management of RC tears from clinical studies available in the literature.METHODS We conducted independent and duplicate electronic database searches including PubMed,Embase,Reference Citation Anallysis,Web of Science,and Cochrane Library in August 2021 for studies analyzing the efficacy and safety of cellular therapy(CT)utilizing MSCs in the management of RC tears.Visual Analog Score(VAS)score for pain,American Shoulder and Elbow Surgeons(ASES)score,Disability of the Arm,Shoulder,and Hand score,Constant score,radiological assessment of healing,and complications such as retear rate and adverse events were the outcomes analyzed.Analysis was performed in R-platform using OpenMeta[Analyst]software.RESULTS Six studies involving 238 patients were included for analysis.We noted a significant reduction in VAS score for pain at 3 mo(weighed mean difference[WMD]=-2.234,P<0.001)and 6 mo(WMD=-3.078,P<0.001)with the use of CT,which was not maintained at long-term follow-up(WMD=-0.749,P=0.544).Concerning functional outcomes,utilization of CT produced a significant shortterm improvement in the ASES score(WMD=17.090,P<0.001)and significant benefit in functional scores such as Constant score(WMD=0.833,P=0.760)at long-term follow-up.Moreover,we also observed significantly improved radiological tendon healing during the longterm follow-up(odds ratio[OR]=3.252,P=0.059).We also noted a significant reduction in the retear rate upon utilization of CT in RC tears both at short-(OR=0.079,P=0.032)and long-term(OR=0.434,P=0.027)follow-ups.We did not observe any significant increase in the adverse events directly related to cellular therapy,as compared with the control group(OR=0.876,P=0.869).CONCLUSION Based on our comprehensive and critical review,we could observe that the utilization of CT in RC tear significantly reduced pain severity at 3 and 6 mo,improved short-term functional outcome,enhanced radiological tendon healing,and mitigated retear rates at both short-and long-term follow-ups.The literature also confirmed the relative safety of using MSC therapy in patients presenting with RC tears.