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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. The investigational advanced therapy medicinal product (ATMP) was expanded under the same protocol in all four countries, and approved by each National Competent Authority., Findings: With safety as primary end-point, no severe adverse event was reported as related to the BM-hMSC. With feasibility as secondary end-point, the participating production centres manufactured the BM-hMSC as planned. The ATMP combined to the bioceramic was surgically delivered to the non-unions, and 26/28 treated patients were found radiologically healed at one year (3 out of 4 cortices with bone bridging)., Interpretation: Safety and feasibility were clinically proven for surgical implantation of expanded autologous BM-hMSC with bioceramic., Funding: EU-FP7-HEALTH-2009, REBORNE Project (GA: 241876)., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Unlabelled: Evidence from animal models replicating postradical prostatectomy erectile dysfunction (pRP-ED) suggests intracavernous injection of bone marrow-mononuclear cells (BM-MNCs) as a promising treatment approach for pRP-ED. We conducted a phase 1/2 pilot clinical trial of intracavernous autologous BM-MNC injection to treat pRP-ED (NCT01089387). Twelve patients with localized prostate cancer and vasculogenic pRP-ED refractory to maximal medical treatment were divided into four equal groups treated with escalating BM-MNC doses (2×10(7), 2×10(8), 1×10(9), 2×10(9)). Tolerance was the primary endpoint. Secondary endpoints were the effects on erectile function and penile vascularization at 6 mo, as assessed using the International Index of Erectile Function-15 and Erection Hardness Scale questionnaires, and color duplex Doppler ultrasound. We measured the peak systolic velocity in cavernous arteries and assessed endothelial function using the penile nitric oxide release test. No serious side effects occurred. At 6 mo versus baseline, significant improvements of intercourse satisfaction (6.8±3.6, 3.9±2.5, p=0.044) and erectile function (17.4±8.9, 7.3±4.5, p=0.006) domains of the International Index of Erectile Function-15 and Erection Hardness Scale (2.6±1.1, 1.3±0.8, p=0.008) were observed in the total population. Spontaneous erections showed significantly greater improvement with the higher doses. Clinical benefits were associated with improvement of peak systolic velocity and of % penile nitric oxide release test and sustained after 1 yr. Our results need to be confirmed by phase 2 clinical trials., Patient Summary: We report a phase 1/2 pilot clinical trial investigating cell therapy with injection of bone marrow mononucleated cells to treat postradical prostatectomy erectile dysfunction. No serious side effects occurred. Improvements of erectile function and penile vascularization were noted. Further studies are required to confirm these preliminary results., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: Hip osteonecrosis is a pathological condition resulting from cellular impairment due to reduction in osteoblast activity and local mesenchymal stem cell populations. Cell-based therapies might aid in overcoming these deficiencies by providing stem cells and other progenitor cells to potentially improve the local cellular environment in the affected hip., Methods: A PubMed search, using the search terms "hip osteonecrosis" and "mesenchymal stem cells", was conducted in December 2013. A total of 15 publications were identified and reviewed for clinical outcomes., Findings: Clinical studies of patients with osteonecrosis treated with mesenchymal stem cells showed beneficial effects. No unexpected adverse events were identified in these studies. Core decompression was the usual method for autologous bone marrow cell implantation into the femoral head. However, other methods have been used such as arterial or venous delivery. A rationale for the use of cytotherapy, as well as the different descriptions of the techniques of implantation MSCs (autologous vs. allogenic, concentration vs. expansion), is provided in the context of treating hip osteonecrosis. Current problems and future challenges with cytotherapy and associated techniques are discussed. This article is part of a Special Issue entitled "Stem Cells and Bones"., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Cord blood units are now routinely used as an alternative source of haematopoietic stem cells from unrelated donors for allogeneic transplantation. In France, cord blood units are collected in a network of more than 70 maternity hospitals in relationship with 11 public cord blood banks part of the Réseau Français de Sang Placentaire. Unrelated cord blood unit donation is an altruistic act, anonymous and free. Donors are selected on medical criteria. Then, only cord blood unit containing more than 100 × 10(7) total nucleated cells and more than 1.8 × 10(6) CD34+ cells are cryopreserved according to Réseau Français de Sang Placentaire recommendations. Cord blood units qualification will be completed by viral and functional testings and the clinical outcome of the newborn child 6 weeks after the collection. Since the last 5 years, cord blood banking growing in France in order to enhance the French registry of volunteer donors by increasing both the number and diversity of the donors listed and make available cord blood banking for transplantation., (Copyright © 2013. Published by Elsevier SAS.)

Mesenchymal stromal cells are defined as non-hematopoietic progenitors characterised by their adherence to plastic in culture, their expression of non-specific markers and their differentiation potential into cells of mesodermic lineage. Resident in numerous tissues, mesenchymal stromal cells are now available from several sources, including both adult and foetal tissues. After their administration, mesenchymal stromal cells preferentially migrate to injured tissues. Mesenchymal stromal cells have therapeutic effects in numerous animal models of tissue injury by a mechanism not yet clearly understood. Mechanisms likely involved in repair can be the production of paracrine, anti-inflammatory and anti-apoptotic factors, as well as cell replacement by their differentiation potential. Mesenchymal stromal cells possess immunosuppressive properties on both innate and adaptative immunity in vitro and in animal models of autoimmunity. Currently their immunosuppressive properties allow testing of mesenchymal stromal cells in allogenic context, although this use requires further investigations. Mesenchymal stromal cells can be isolated and expanded in vitro in clinical grade conditions. They represent a promising candidate for the cellular therapy of diseases, such as acute myocardial infarction, diabetes, graft versus host disease or neurodegenerative diseases. Critical points including the standardization of production and long term toxicity have to be resolved before their large scale use in clinical conditions., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Culture of expanded mesenchymal stem cells (MSCs) seeded on biomaterials may represent a clinical alternative to autologous bone graft in bone regeneration. Foetal bovine serum (FBS) is currently used for MSC expansion, despite risks of infectious disease transmission and immunological reaction due to its xenogenic origin. This study aimed to compare the osteogenic capacities of clinical-grade human MSCs cultured with FBS or allogenic human platelet lysate (PL). In vitro, MSCs cultured in PL both accelerate the expansion rate over serial passages and spontaneously induce osteoblastic gene expression such as alkaline phosphatase (ALP), bone sialoprotein (BSP), osteopontin (Op) and bone morphogenetic protein-2 (BMP-2). In vivo, ectopic bone formation is only observed on ceramics seeded with MSCs grown in PL medium implanted under the skin of immunodeficient mice for 7 weeks. In conclusion, allogenic human PL accelerates MSC proliferation and enhances MSC osteogenic differentiation.