Dual inhibition of P38 MAPK and JNK pathways preserves stemness markers and alleviates premature activation of muscle stem cells during isolation.

Background: Adult skeletal muscle contains resident muscle stem cells (MuSC) with high myogenic and engraftment potentials, making them suitable for cell therapy and regenerative medicine approaches. However, purification process of MuSC remains a major hurdle to their use in the clinic. Indeed, muscle tissue enzymatic dissociation triggers a massive activation of stress signaling pathways, among which P38 and JNK MAPK, associated with a premature loss of MuSC quiescence.

Mesenchymal Stem Cell Therapy for Bone Repair of Human Hip Osteonecrosis with Bilateral Match-Control Evaluation: Impact of Tissue Source, Cell Count, Disease Stage, and Volume Size on 908 Hips.

We investigated the impact of mesenchymal stem cell (MSC) therapy on treating bilateral human hip osteonecrosis, analyzing 908 cases. This study assesses factors such as tissue source and cell count, comparing core decompression with various cell therapies. This research emphasizes bone repair according to pre-treatment conditions and the specificities of cell therapy in osteonecrosis repair, indicating a potential for improved bone repair strategies in hips without femoral head collapse.

Prognosis of hip osteonecrosis after cell therapy with a calculator and artificial intelligence: ten year collapse-free survival prediction on three thousand and twenty one hips.

Purpose: Several reports have identified prognostic factors for hip osteonecrosis treated with cell therapy, but no study investigated the accuracy of artificial intelligence method such as machine learning and artificial neural network (ANN) to predict the efficiency of the treatment. We determined the benefit of cell therapy compared with core decompression or natural evolution, and developed machine-learning algorithms for predicting ten year collapse-free survival in hip osteonecrosis treated with cell therapy. Using the best algorithm, we propose a calculator for "prognosis hip osteonecrosis cell therapy (PHOCT)" accessible for clinical use.

Ankle osteonecrosis in fifty-one children and adolescent's leukemia survivors: a prospective randomized study on percutaneous mesenchymal stem cells treatment.

Purpose: Corticoid treatment associated with haematologic treatments can lead to ankle osteonecrosis in children's survivors of acute leukemia (ALL). Based on the efficiency of mesenchymal stem cells (MSCs) in hip osteonecrosis, we performed an evaluation of this treatment in 51 children and adolescents who had symptomatic ankle osteonecrosis after therapy for haematologic cancer.

Material And Methods: The 51 patients had a total of 79 osteonecrosis sites on MRI, with 29 talus sites, 18 metaphyseal tibia sites, 12 epiphyseal tibia sites, eight calcaneus sites, six fibula sites, four navicular sites, and two cuboid sites.

Progressive and Coordinated Mobilization of the Skeletal Muscle Niche throughout Tissue Repair Revealed by Single-Cell Proteomic Analysis.

Skeletal muscle is one of the only mammalian tissues capable of rapid and efficient regeneration after trauma or in pathological conditions. Skeletal muscle regeneration is driven by the muscle satellite cells, the stem cell population in interaction with their niche. Upon injury, muscle fibers undergo necrosis and muscle stem cells activate, proliferate and fuse to form new myofibers.

Osteonecrosis of the Femoral Head Safely Healed with Autologous, Expanded, Bone Marrow-Derived Mesenchymal Stromal Cells in a Multicentric Trial with Minimum 5 Years Follow-Up.

: Osteonecrosis (ON) of the femoral head represents a potentially severe disease of the hip where the lack of bone regeneration may lead to femoral head collapse and secondary osteoarthritis, with serious pain and disability. The aim of this European, multicentric clinical trial was to prove safety and early efficacy to heal early femoral head ON in patients through minimally invasive surgical implantation of autologous mesenchymal stromal cells (MSC) expanded from bone marrow (BM) under good manufacturing practices (GMP). : Twenty-two patients with femoral head ON (up to ARCO 2C) were recruited and surgically treated in France, Germany, Italy and Spain with BM-derived, expanded autologous MSC (total dose 140 million MSC in 7 mL).

Early injection of autologous bone marrow concentrates decreases infection risk and improves healing of acute severe open tibial fractures.

Introduction: Open fractures are at risk of nonunion; surgeons are reluctant to propose early standard bone grafting after open fractures, preferring to wait in order to adequately assess the facture status of infection. Bone marrow contains mesenchymal stem cells (MSCs) and granulocyte and macrophage precursors identified in vitro as colony forming units-granulocyte macrophage (CFU-GM), both of which have a prophylactic action against infection. We therefore tested the hypothesis that early injection of bone marrow concentrate would be useful in these fractures.

Cell therapy for posttraumatic shoulder osteonecrosis.

Purpose: This study compared the clinical and radiological results of bone marrow mesenchymal stem cell implantation with traditional simple core decompression (CD) using a matched pair case-control design for osteonecrosis of the humeral head (ONHH) after fracture of the proximal humerus.

Patients: We retrospectively reviewed 64 patients who had surgery for ONHH. Thirty patients had been treated with cell therapy between 2010 and October 2015, with 18 patients at pre-collapse stage (8 stages-I, 10 stages-II), and 12 patients at post-collapse stages (7 stages-III and 5 stages-IV).

Cell therapy for post-traumatic hip osteonecrosis in young patients.

Purpose: To investigate the effects of mesenchymal stem cells injections for treatment of post-traumatic osteonecrosis of the femoral head.

Methods: A total of 46 patients were eligible and enrolled in the study. Twenty-three patients were treated with cell therapy and 23 patients with hip arthroplasty (control group).

Distinct Phases of Postnatal Skeletal Muscle Growth Govern the Progressive Establishment of Muscle Stem Cell Quiescence.

Muscle stem cells (or muscle satellite cells [MuSCs]) are required for postnatal growth. Yet, the detailed characterization of myogenic progression and establishment of quiescence during this process remains poorly documented. Here, we provide an overview of myogenic cells heterogeneity and dynamic from birth to adulthood using flow cytometry.

Subchondral bone or intra-articular injection of bone marrow concentrate mesenchymal stem cells in bilateral knee osteoarthritis: what better postpone knee arthroplasty at fifteen years? A randomized study.

Purpose: There is an increasing number of reports on the treatment of knee osteoarthritis (OA) using mesenchymal stem cells (MSCs). However, it is not known what would better drive osteoarthritis stabilization to postpone total knee arthroplasty (TKA): targeting the synovial fluid by injection or targeting on the subchondral bone with MSCs implantation.

Methods: A prospective randomized controlled clinical trial was carried out between 2000 and 2005 in 120 knees of 60 patients with painful bilateral knee osteoarthritis with a similar osteoarthritis grade.

Early efficacy evaluation of mesenchymal stromal cells (MSC) combined to biomaterials to treat long bone non-unions.

Background And Study Aim: Advanced therapy medicinal products (ATMP) frequently lack of clinical data on efficacy to substantiate a future clinical use. This study aims to evaluate the efficacy to heal long bone delayed unions and non-unions, as secondary objective of the EudraCT 2011-005441-13 clinical trial, through clinical and radiological bone consolidation at 3, 6 and 12 months of follow-up, with subgroup analysis of affected bone, gender, tobacco use, and time since the original fracture.

Patients And Methods: Twenty-eight patients were recruited and surgically treated with autologous bone marrow derived mesenchymal stromal cells expanded under Good Manufacturing Practices, combined to bioceramics in the surgical room before implantation.

Human Apoptotic Cells, Generated by Extracorporeal Photopheresis, Modulate Allogeneic Immune Response.

The induction of specific and sustainable tolerance is a challenging issue in organ transplantation. The discovery of the immunosuppressive properties of apoptotic cells in animal models has paved the way for their use in human transplantation. In this work, we aimed to define a stable, reproducible, and clinically compatible production procedure of human apoptotic cells (Apo-cells).

Long-Term Results of Cultured Limbal Stem Cell Versus Limbal Tissue Transplantation in Stage III Limbal Deficiency.

We aimed to evaluate efficiency and safety of transplantation of limbal stem cells (LSC) cultured on human amniotic membrane with no feeders and to compare cultured LSC with limbal tissue transplantation. Thirty eyes with stage III LSC deficiency were treated with autologous (autoLSC) or allogeneic (alloLSC) cultured LSC transplantation (prospective phase II clinical trial; average follow-up time, 72 months) or autologous (autoLT) or allogeneic (alloLT) limbal tissue transplantation (retrospective control group; average follow-up time, 132 months) between 1993 and 2014. The 5-year graft survival defined by absence of recurrence of the clinical signs of limbal deficiency was 71% for autoLSC, 0% for alloLSC, 75% for autoLT, and 33% for alloLT.

Design and Validation of an Automated Process for the Expansion of Peripheral Blood-Derived CD34 Cells for Clinical Use After Myocardial Infarction.

We previously demonstrated that intracardiac delivery of autologous peripheral blood-derived CD34 stem cells (SCs), mobilized by granulocyte-colony stimulating factor (G-CSF) and collected by leukapheresis after myocardial infarction, structurally and functionally repaired the damaged myocardial area. When used for cardiac indication, CD34 cells are now considered as Advanced Therapy Medicinal Products (ATMPs). We have industrialized their production by developing an automated device for ex vivo CD34 -SC expansion, starting from a whole blood (WB) sample.

Feasibility of Bioengineered Tracheal and Bronchial Reconstruction Using Stented Aortic Matrices.

Importance: Airway transplantation could be an option for patients with proximal lung tumor or with end-stage tracheobronchial disease. New methods for airway transplantation remain highly controversial.

Objective: To establish the feasibility of airway bioengineering using a technique based on the implantation of stented aortic matrices.

History of concentrated or expanded mesenchymal stem cells for hip osteonecrosis: is there a target number for osteonecrosis repair?

Purpose: Despite multiple possible treatments, the risk of collapse remains the main problem of osteonecrosis. Heart failure (HF). In an effort to address the reverse this issue, curative strategies with regenerative medicine are increasingly being considered.

Cell therapy versus simultaneous contralateral decompression in symptomatic corticosteroid osteonecrosis: a thirty year follow-up prospective randomized study of one hundred and twenty five adult patients.

Purpose: Symptomatic osteonecrosis related to corticosteroids has a high risk of progression to collapse in absence of treatment. The purposes of this study were to evaluate the results of autologous bone marrow grafting of the symptomatic hip in adult patients with osteonecrosis and to compare the results with core decompression alone in the contralateral symptomatic hip.

Materials And Methods: A total of 125 consecutive patients (78 males and 47 females) with bilateral osteonecrosis (ON) and who had both hips symptomatic and at the same stage on each side (stage I or II) were included in this study from 1988 to 1998.

Feasibility and safety of treating non-unions in tibia, femur and humerus with autologous, expanded, bone marrow-derived mesenchymal stromal cells associated with biphasic calcium phosphate biomaterials in a multicentric, non-comparative trial.

Background: ORTHO-1 is a European, multicentric, first in human clinical trial to prove safety and feasibility after surgical implantation of commercially available biphasic calcium phosphate bioceramic granules associated during surgery with autologous mesenchymal stromal cells expanded from bone marrow (BM-hMSC) under good manufacturing practices, in patients with long bone pseudarthrosis.

Methods: Twenty-eight patients with femur, tibia or humerus diaphyseal or metaphyso-diaphyseal non-unions were recruited and surgically treated in France, Germany, Italy and Spain with 100 or 200 million BM-hMSC/mL associated with 5-10 cc of bioceramic granules. Patients were followed up during one year.

Subchondral stem cell therapy versus contralateral total knee arthroplasty for osteoarthritis following secondary osteonecrosis of the knee.

Purpose: Total knee arthroplasty (TKA) implanted in patients with secondary osteonecrosis (ON) related to corticosteroids have relatively poor outcome (20% revision rate) at a mean follow-up of only eight years. With the hypothesis that subchondral bone marrow injection might improve knees in these patients, we evaluated 30 patients who had bilateral knee osteoarthritis with severe joint space narrowing and received TKA in one knee and subchondral bone marrow concentrate injection in the contralateral knee.

Material And Methods: A prospective randomized controlled clinical trial was carried out in 60 knees of 30 patients (mean age 28 years, 18-41) who presented bilateral osteoarthritis secondary to knee ON related to corticosteroids in relation with different severe medical conditions.