Bio-Medical Materials and Engineering - Volume 28, issue s1

Article Type: Other

Citation: Bio-Medical Materials and Engineering, vol. 28, no. s1, pp. iii-iii, 2017

Authors: Stoltz, J.F. | Magdalou, J. | Bensoussan, D.

Article Type: Other

DOI: 10.3233/BME-171618

Citation: Bio-Medical Materials and Engineering, vol. 28, no. s1, pp. S1-S2, 2017

Authors: Ferry, Nicolas

Article Type: Research Article

Abstract: The regulation for the use of stem cells has evolved during the past decade with the aim of ensuring a high standard of quality and safety for human derived products throughout Europe to comply with the provision of the Lisbon treaty. To this end, new regulations have been issued and the regulatory status of stem cells has been revised. Indeed, stem cells used for therapeutic purposes can now be classified as a cell preparation, or as advanced therapy medicinal products depending on the clinical indication and on the procedure of cell preparation. Furthermore, exemptions to the European regulation are applicable …for stem cells prepared and used within the hospital. The aim of this review is to give the non-specialized reader a broad overview of this particular regulatory landscape. Show more

Keywords: European regulation, Advanced Therapy Medicinal Products (ATMP), somatic cell therapy, tissue engineering

DOI: 10.3233/BME-171619

Citation: Bio-Medical Materials and Engineering, vol. 28, no. s1, pp. S3-S7, 2017

Authors: Elzaabi, Mazen | Thevenin, Agnès | Lirsac, Pierre-Noël

Article Type: Research Article

Abstract: CELLfor CURE is a French Contract Development and Manufacturing Organization (CDMO) dedicated to industrialization and process development for routine manufacturing, GMP manufacturing for clinical and commercial batches and regulatory services and associated logistics. CELLfor CURE is a subsidiary of LFB Group. Stem cells fields of application gather cell and gene therapy as well as tissue engineering. According to VisionGain survey, cell therapy medicinal products will remain predominant in the future. Clinical trials are sponsored either by universities or private companies. Most of clinical trials are performed in oncology (53%). More than 100 clinical trials are currently performed in …France, involving 36 products in clinical phases II or II/III. Tomorrow’s regenerative medicine will be organ reconstruction using scaffolds and bioprinting technologies. The expected applications in the near future could be skin, cornea, blood vessels, retina, urethra and trachea. There are still important issues to overcome: create the vasculature and neuron connection. Solutions are expected regarding I) fundamental biology, in particular better understanding of IPS behavior and metabolism, precursor differentiation conditions, sustainability of induced genetic changes, II) technical approaches which involves injectable preservation medium, high density cells and centrifugation system. Show more

Keywords: LFB, CELLforCURE, gene therapy, cell therapy, Contract Development and Manufacturing Organization

DOI: 10.3233/BME-171620

Citation: Bio-Medical Materials and Engineering, vol. 28, no. s1, pp. S9-S13, 2017

Authors: George, Daniel | Spingarn, Camille | Dissaux, Caroline | Nierenberger, Mathieu | Rahman, Ranya Abdel | Rémond, Yves

Article Type: Research Article

Abstract: Predictive theoretical–numerical modeling of the behavior and evolution of biological tissue is a difficult task since many of the required knowledge tools (experimental, theoretical and numerical) are still not well understood. We present here some methodologies and results specific to multiscale and multiphysics numerical modeling of biological tissues applied to the predictive behavior of cortical veins depending on their local constituents’ microstructure and for bone remodeling and reconstruction as a function of the local mechanobiology. Although further work is required to improve the accuracy of the developed models, the proposed approaches highlight their potential usefulness for understanding the mechanical-biological couplings, …short and long term predictions of biological evolutions as well as possible further transfer to medical applications. Show more

Keywords: Multiscale, mechanobiology, numerical modeling, homogenization, vein, bone

DOI: 10.3233/BME-171621

Citation: Bio-Medical Materials and Engineering, vol. 28, no. s1, pp. S15-S27, 2017

Authors: Han, Z.C. | Du, W.J. | Han, Z.B. | Liang, L.

Article Type: Research Article

Abstract: Mesenchymal stem cells (MSCs) are being tested in several biological systems and clinical settings with the aim of exploring their therapeutic potentials for a variety of diseases. MSCs are also known to be heterogeneous populations with variable functions. In the context of this multidimensional complexity, a recurrent question is what source or population of MSCs is suitable for specific clinical indications. Here, we reported that the biological features of MSCs varied with the individual donor, the tissue source, the culture condition and the subpopulations. Placental chorionic villi (CV) derived MSCs exhibited superior activities of immunomodulation and pro-angiogenesis compared to MSCs …derived from bone marrow (BM), adipose and umbilical cord (UC). We identified a subpopulation of CD106(VCAM-1)+ MSCs, which are present richly in placental CV, moderately in BM, and lowly in adipose and UC. The CD106+ MSCs possess significantly increased immunomodutory and pro-angiogenic activities compared to CD106− MSCs. Analysis of gene expression and cytokine secretion revealed that CD106+ MSCs highly expressed several immnumodulatory and pro-angiogenic cytokines. Our data offer new insights on the identification and selection of suitable source or population of MSCs for clinical applications. Further efforts should be concentrated on standardizing methods which will ultimately allow the validation of MSC products with defined biomarkers as predictive of potency in suitable pre-clinical models and clinical settings. Show more

Keywords: Mesenchymal stem cells, heterogeneity, immunomodulation, angiogenesis, hematopoiesis, biomarkers

DOI: 10.3233/BME-171622

Citation: Bio-Medical Materials and Engineering, vol. 28, no. s1, pp. S29-S45, 2017

Authors: Huselstein, Céline | Rahouadj, R. | de Isla, N. | Bensoussan, D. | Stoltz, J.F. | Li, Y.P.

Article Type: Research Article

Abstract: Thanks to their immune properties, the mesenchymal stem cells (MSC) are a promising source for cell therapy. Current clinical trials show that MSC administrated to patients can treat different diseases (graft-versus-host disease (GVHD), liver cirrhosis, systemic lupus, erythematosus, rheumatoid arthritis, type I diabetes… ). In this case, the most common mode of cell administration is the intravenous injection, and the hemodynamic environment of cells induced by blood circulation could interfere on their behavior during the migration and homing towards the injured site. After a brief review of the mechanobiology concept, this paper will help in understanding how …the mechanical environment could interact with MSC behavior once they are injected to patient in cell-based treatment. Show more

Keywords: Mesenchymal stem cells, cell-based treatment, mechanobiology, migration, homing

DOI: 10.3233/BME-171623

Citation: Bio-Medical Materials and Engineering, vol. 28, no. s1, pp. S47-S56, 2017

Authors: Charif, N. | Li, Y.Y. | Targa, L. | Zhang, L. | Ye, J.S. | Li, Y.P. | Stoltz, J.F. | Han, H.Z. | de Isla, N.

Article Type: Research Article

Abstract: With their proliferation, differentiation into specific cell types, and secretion properties, mesenchymal stromal/stem cells (MSC) are very interesting tools to be used in regenerative medicine. Bone marrow (BM) was the first MSC source characterized. In the frame of autologous MSC therapy, it is important to detect donor’s parameters affecting MSC potency. Age of the donors appears as one parameter that could greatly affect MSC properties. Moreover, in vitro cell expansion is needed to obtain the number of cells necessary for clinical developments. It will lead to in vitro cell aging that could modify cell properties. This review recapitulates …several studies evaluating the effect of in vitro and in vivo MSC aging on cell properties. Show more

Keywords: Mesenchymal stromal/stem cells, bone marrow, aging, regenerative medicine

DOI: 10.3233/BME-171624

Citation: Bio-Medical Materials and Engineering, vol. 28, no. s1, pp. S57-S63, 2017

Authors: Ferratge, S. | Boyer, J. | Arouch, N. | Chevalier, F. | Uzan, G.

Article Type: Research Article

Abstract: Endothelial Colony Forming Cells (ECFCs) are obtained in culture from Circulating Endothelial Progenitor Cells. They display all characteristics of endothelial cells and they display stem cells features. Cord blood-derived ECFCs (CB-ECFCs) have a high clonogenic and proliferative potentials, and exhibit vascular repair capabilities useful for the treatment of ischemic diseases. However, the link between immaturity and functional properties of CB-ECFCs is still poorly defined. We showed that these cells have a high clonogenic potential and are capable to be efficiently reprogrammed into induced pluripotent stem cells. Moreover, we analyzed the expression of a broad panel of genes involved in embryonic …stem cell properties. We define a novel stem cell transcriptional signature for CB-ECFCs fora better characterization and stratification according to their stem cell profile. We then improved the yield of CB-ECFC production for obtaining cells more functional in fewer passages. We used Glycosaminoglycans (GAG), components from the extracellular matrix which potentiate heparin binding growth factor activities. GAG mimetics were designed, having the capacity to increase the yield of ECFC during the isolation process, to increase the number of colonies, improve adhesion, proliferation, migration and self-renewal. GAG mimetics have thus great interest for vascular regeneration in combination with ECFC. Our results show that CB-ECFC are immature cells harboring specific functions such as formation of colonies, proliferation and formation of vascular structures in vitro and in vivo . Show more

Keywords: Vascular repair, circulating endothelial progenitors, plasticity, stem cells

DOI: 10.3233/BME-171625

Citation: Bio-Medical Materials and Engineering, vol. 28, no. s1, pp. S65-S74, 2017

Authors: Dostert, G. | Willemin, A.-S. | Jouan-Hureaux, V. | Louis, H. | Hupont, S. | Gillet, P. | Menu, P. | Decot, V. | Moby, V. | Velot, É.

Article Type: Research Article

Abstract: Mesenchymal stem cells (MSCs) are a common tool in regenerative medicine. The nanoscale extracellular vesicles (nEVs) secreted by these cells were recently brought up to light thanks to their therapeutic potential. In this study, we assessed the in vitro behaviour of human umbilical vein endothelial cells (HUVECs) exposed to nEVs derived from human umbilical cord mesenchymal stem cells (hUC-MSCs). Nanoscale extracellular vesicles were isolated and characterized by NanoSight® and flow cytometry. HUVECs were stimulated with various concentrations of nEVs. To assess nEV interactions with HUVECs, confocal microscopy and angiogenesis assay were performed. The use of nEVs derived from …hUC-MSCs was able to produce positive outcomes on HUVECs by acting on their angiogenic potential. Show more

Keywords: Nanoscale extracellular vesicles, HUVECs, human umbilical cord MSCs, angiogenesis

DOI: 10.3233/BME-171626

Citation: Bio-Medical Materials and Engineering, vol. 28, no. s1, pp. S75-S79, 2017