BackgroundKnee osteoarthritis (KOA) is a major health problem especially in the aging population. There is a need for safe treatment that restores the cartilage and reduces the symptoms. The use of stem cells is emerging as a possible option for the moderate and severe cases. This study aimed at testing the safety of autologous bone marrow mesenchymal stem cells (BM-MSCs) expanded in vitro when given intra-articularly to patients with stage II and III KOA. As a secondary end point, the study tested the ability of these cells to relieve symptoms and restore the knee cartilage in these patients as judged by normalized knee injury and Osteoarthritis Outcome Score (KOOS) and by magnetic resonance imaging (MRI).MethodsThirteen patients with a mean age of 50 years suffering from KOA stages II and III were given two doses of BM-MSCs 1 month apart totaling 61 × 106 ± 0.6 × 106 by intra-articular injection in a phase I prospective clinical trial. Each patient was followed for a minimum of 24 months for any adverse events and for clinical outcome using normalized KOOS. Cartilage thickness was assessed by quantitative MRI T2 at 12 months of follow-up.ResultsNo severe adverse events were reported up to 24 months follow-up. Normalized KOOS improved significantly. Mean knee cartilage thickness measured by MRI improved significantly.ConclusionBM-MSCs given intra-articularly are safe in knee osteoarthrosis. Despite the limited number of patients in this study, the procedure described significantly improved the KOOS and knee cartilage thickness, indicating that they may enhance the functional outcome as well as the structural component.Trial registrationClinicalTrials.gov, NCT02118519

We report about rationally designed ultrashort peptide bioinks, overcoming severe limitations in current bioprinting procedures. Bioprinting is increasingly relevant in tissue engineering, regenerative and personalized medicine due to its ability to fabricate complex tissue scaffolds through an automated deposition process. Printing stable large-scale constructs with high shape fidelity and enabling long-term cell survival are major challenges that most existing bioinks are unable to solve. Additionally, they require chemical or UV-cross-linking for the structure-solidifying process which compromises the encapsulated cells, resulting in restricted structure complexity and low cell viability. Using ultrashort peptide bioinks as ideal bodylike but synthetic material, we demonstrate an instant solidifying cellembedding printing process via a sophisticated extrusion procedure under true physiological conditions and at cost-effective low bioink concentrations. Our printed large-scale cell constructs and the chondrogenic differentiation of printed mesenchymal stem cells point to the strong potential of the peptide bioinks for automated complex tissue fabrication.

SummaryAimsThis open‐label prospective phase I/IIa clinical study used autologous bone marrow‐derived mesenchymal stromal cells (BM‐MSCs) followed by mesenchymal stromal cells conditioned media (MSC‐CM) for the first time to treat multiple sclerosis (MS) patients. The primary goal was to assess the safety and feasibility and the secondary was efficacy. The correlation between the MSC‐CM content and treatment outcome was investigated.MethodsTen MS patients who failed conventional therapy were enrolled. Adverse events were recorded to assess safety. The Expanded Disability Status Scale (EDSS) was the primary efficacy measurement, the secondary included clinical (25WFT, 9‐PHT), cognitive (MMS), ophthalmology (OCT, VEP), and radiological (MRI lesion and volume) tests. The MSCs‐CM concentration of 27 inflammatory biomarkers was investigated.ResultsThe treatment protocol was well tolerated by patients. There was an overall trend of improvement in all the tests, except the lesion volume which increased significantly. A decrease of 4 and 3.5 points on the EDSS was achieved in two patients. We report a correlation between a decreased lesion number at baseline and higher IL‐6, IL‐8, and VEGF MSC‐CM content.ConclusionThe used protocol was safe and feasible with possible efficacy. The addition of MSC‐CM could be related to the magnitude of EDSS improvement observed.

Aim: Variations in the clinical outcomes using mesenchymal stem cells (MSCs) treatments exist, reflecting different origins and niches. To date, there is no consensus on the best source of MSCs most suitable to treat a specific disease. Methods: Total transcriptome analysis of human MSCs was performed. MSCs were isolated from two adult sources bone marrow, adipose tissue and two perinatal sources umbilical cord and placenta. Results: Each MSCs type possessed a unique expression pattern that reflects an advantage in terms of their potential therapeutic use. Advantages in immune modulation, neurogenesis and other aspects were found. Discussion: This study is a milestone for evidence-based choice of the type of MSCs used in the treatment of diseases.

Long-standing foot ulcers present a great challenge in diabetes care. Platelet products have been suggested as a possible therapeutic option. However, nor the effect of an injectable form of platelet lysate on the healing of ulcers nor that on primary cells of the epidermis have been studied. In the current study, we present two cases of an ongoing clinical trial showing the positive effect of autologous platelet lysate injected perilesional. Both clinical cases treated with injections of hPL showed complete healing of previously un-healed within 8 weeks of treatment. Further, we describe the in vitro effect of human platelet lysate (hPL) on primary human epidermal keratinocytes (HEK) in terms of chemotaxis, migration and proliferation. In vitro, HEK showed enhanced chemotaxis towards the hPL compared to keratinocyte-defined media (p < 0.0001). Their migration was also stimulated especially at hPL concentration of 10%V/V (p < 0.0001). In contrast, hPL significantly inhibited HEK proliferation measured through MTT assay (p < 0.0001). In conclusion, the findings presented here provide preliminary evidence of an explanatory mechanism for the effect of hPL on primary keratinocytes and therefore of their potential use in a clinical setting. hPL promotes keratinocyte migration and therefore closure of foot ulcers.