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Hematopoietic stem and progenitor cells (HSPC) reside in the bone marrow (BM) niche and serve as a reservoir for mature blood cells throughout life. Aging in the BM is characterized by low-grade chronic inflammation that could contribute to the reduced functionality of aged HSPC. Mesenchymal stromal cells (MSC) in the BM support HSPC self-renewal. However, changes in MSC function with age and the crosstalk between MSC and HSPC remain understudied. Here, we conducted an extensive characterization of senescence features in BM-derived MSC from young and aged healthy donors. Aged MSC displayed an enlarged senescent-like morphology, a delayed clonogenic potential and reduced proliferation ability when compared to younger counterparts. Of note, the observed proliferation delay was associated with increased levels of SA-β-galactosidase (SA-β-Gal) and lipofuscin in aged MSC at early passages and a modest but consistent accumulation of physical DNA damage and DNA damage response (DDR) activation. Consistent with the establishment of a senescence-like state in aged MSC, we detected an increase in pro-inflammatory senescence-associated secretory phenotype (SASP) factors, both at the transcript and protein levels. Conversely, the immunomodulatory properties of aged MSC were significantly reduced. Importantly, exposure of young HSPC to factors secreted by aged MSC induced pro-inflammatory genes in HSPC and impaired HSPC clonogenic potential in a SASP-dependent manner. Altogether, our results reveal that BM-derived MSC from aged healthy donors display features of senescence and that, during aging, MSC-associated secretomes contribute to activate an inflammatory transcriptional program in HSPC that may ultimately impair their functionality., (© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Objective: The purpose of this study was to investigate the potential ability of autologous conditioned serum (ACS) to decrease pain and improve joint functionality in patients affected by knee osteoarthritis (OA). Methods: Fifteen patients with clinical and radiological signs of OA of the knee were recruited for this study. Each patient received 4 injections of ACS (Orthokine; orthogen, Dusseldorf, Germany) at the site of OA once per week for 4weeks. Clinical and functional evaluation was performed using the VAS scale for pain, WOMAC scale and KSS functional and clinical scores before the first injection, at one week, at two weeks, at three weeks, at one month and at six months. Statistical analysis was done with the Wilcoxon Signed-Rank Test. Results: Our results show an improvement of all the evaluation scales at 6months follow-up. Particularly, VAS scales among all patients decreased by 35.8% (p=.00148), KSS functional scores improved by 38.2% (p=.00148), KSS clinical scores improved by 28.9% (p=.00236) and WOMAC scores were reduced by 19.8% (p=.00188). Few adverse effects were observed in our sample. The most common complaint was pain and swelling in the subsequent days after performing the intraarticular injection. Only one patient reported rigidity following the injection of the ACS. Conclusion: Our results, in conjunction with preexisting studies in the medical literature regarding ACS, demonstrate the viability of this therapy for the treatment of knee OA, showing positive influence on pain and joint function without significant adverse effects. [ABSTRACT FROM AUTHOR]