Mesenchymal stem cell (MSC) transplantation has proved to be a promising strategy in cell therapy and regenerative medicine. Although their mechanism of action is not completely clear, it has been suggested that their therapeutic activity may be mediated by a paracrine effect. The main goal of this study was to evaluate by radiographic, morphometric and histological analysis the ability of mesenchymal stem cells derived from human adipose tissue (Ad-MSC) and their conditioned medium (CM), to repair surgical bone lesions using an in vivo model (rabbit mandibles). The results demonstrated that both, Ad-MSC and CM, induce bone regeneration in surgically created lesions in rabbit's jaws, suggesting that Ad-MSC improve the process of bone regeneration mainly by releasing paracrine factors. The evidence of the paracrine effect of MSC on bone regeneration has a major impact on regenerative medicine, and the use of their CM can address some issues and difficulties related to cell transplants. In particular, CM can be easily stored and transported, and is easier to handle by medical personnel during clinical procedures.

Bone defects are the cause of functional disability and the restoration of skeletal function remains an important challenge on orthopedics, neurosurgery and oral and maxillofacial surgery. Because of the limitations of the currently used techniques for the reconstruction of bone defects and the difficulties for the implementation of new therapeutic strategies, a new paradigm in the field of reconstructive surgery has arisen, leading to tissue engineering and regenerative medicine. Mesenchymal stem cells (MSC) have emerged as a promising alternative for the treatment of bone lesions. It was postulated that the therapeutic action was the result of proliferation and differentiation of MSCs, replacing injured tissue. However, recent studies have shown that MSCs secrete a number of trophic factors that have a strong effect during repair and tissue regeneration. This represents a shift from a paradigm centered on MSC proliferation and differentiation to a new paradigm in which the MSCs exert their beneficial effect by the secretion of paracrine factors that induce endogenous repair mechanisms. This chapter will bring together basic and clinical aspects, focused on novel findings on MSC paracrine effect and the development of new therapeutic strategies based on growth factors, cytokines and signaling molecules involved in bone regeneration.

Background Given the limitations of current therapies for the reconstruction of bone defects, regenerative medicine has arisen as a new therapeutic strategy along with mesenchymal stem cells (MSCs), which, because of their osteogenic potential and immunomodulatory properties, have emerged as a promising alternative for the treatment of bone injuries. In vivo studies have demonstrated that MSCs have a positive effect on regeneration due to their secretion of cytokines and growth factors that, when collected in conditioned medium (MSC-CM) and applied to an injured tissue, can modulate and promote the formation of new tissue. Objective To evaluate the effectiveness of application of conditioned medium derived from mesenchymal stem cells in bone regeneration in animal and human models. Methods We conducted a systematic review with a comprehensive search through February of 2018 using several electronic databases (MEDLINE, EMBASE, SCOPUS, CENTRAL (Ovid), and LILACS), and we also used the “snowballing technique”. Articles that met the inclusion criteria were selected through abstract review and subsequent assessment of the full text. We assessed the risk of bias with the SYRCLE and Cochrane tools, and three meta-analyses were performed. Results We included 21 articles, 19 of which used animal models and 2 of which used human models. In animal models, the application of MSC-CM significantly increased the regeneration of bone defects in comparison with control groups. Human studies reported early mineralization in regenerated bones, and no bone resorption, inflammation, nor local or systemic alterations were observed in any case. The meta-analysis showed an overall favorable effect of the application of MSC-CM. Conclusions The application of MSC-CM to bone defects has a positive and favorable effect on the repair and regeneration of bone tissue, particularly in animal models. It is necessary to perform additional studies to support the application of MSC-CM in clinical practice.

Previously, we have developed collagen type I scaffolds including microparticles of gelatin-collagen type I (SGC) that are able to control the release of a hydroglycolic extract of the Calendula officinalis flower. The main goal of the present work was to carry out the preclinical evaluation of SGC alone or loaded with the C. officinalis extract (SGC-E) in a lagomorph model of full-thickness skin wound. A total of 39 rabbits were distributed in three groups, of 13 animals each. The first group was used to compare wound healing by secondary intention (control) with wound healing observed when wounds were grafted with SGC alone. Comparison of control wounds with wounds grafted with SGC-E was performed in the second group, and comparison of wounds grafted with SGC with wounds grafted with SGC-E was performed in the third group. Clinical follow-ups were carried in all animals after surgery, and histological and histomorphometric analyses were performed on tissues taken from the healed area and healthy surrounding tissue. Histological and histomorphometric results indicate that grafting of SGC alone favors wound healing and brings a better clinical outcome than grafting SGC-E. In vitro collagenase digestion data suggested that the association of the C. officinalis extract to SGC increased the SGC-E cross-linking, making it difficult to degrade and affecting its biocompatibility.

Biomédica 2014;34:67-78 Ad-MSC en hidrogeles de plasma sanguíneo humano Contribución de los autores:Itali M. Linero: diseño de experimentos, obtención, cultivo y caracterización de las Ad-MSC, elaboración del hidrogel de plasma sanguíneo humano, escritura y revisión del manuscrito. Adriana Doncel: obtención, cultivo y caracterización de las Ad-MSC, y revisión del manuscrito. Orlando Chaparro: diseño de experimentos, escritura y revisión del manuscrito. Introducción. La utilización de las células madre mesenquimales en la práctica clínica ha aumentado considerablemente en la última década, ya que juegan un papel favorable en los procesos de reparación y regeneración tisular, siendo la principal herramienta de la terapia celular para el tratamiento de enfermedades que afectan funcionalmente el tejido óseo y cartilaginoso. Objetivo. Evaluar la proliferación y capacidad de diferenciación osteogénica in vitro de células madre mesenquimales derivadas de tejido adiposo humano en un hidrogel de plasma sanguíneo. Materiales y métodos. Se obtuvieron células madre mesenquimales a partir de explantes de tejido adiposo humano y se caracterizaron por citometría de flujo; se buscó demostrar su multipotencialidad por su capacidad de diferenciación osteogénica y adipogénica. Se evaluó la proliferación celular y la capacidad de diferenciación osteogénica de las células cultivadas en hidrogeles de plasma sanguíneo.Resultados. Las células madre mesenquimales derivadas de tejido adiposo cultivadas en el hidrogel de plasma sanguíneo humano mostraron un patrón de proliferación muy similar al de las células cultivadas en monocapa y, además, mantuvieron su capacidad de diferenciación hacia el linaje osteogénico. Conclusiones. El hidrogel de plasma sanguíneo humano es un soporte adecuado para que las células madre mesenquimales derivadas de tejido adiposo humano proliferen y se diferencien hacia el linaje osteogénico y constituye un vehículo adecuado para su administración en regeneración del tejido óseo.Palabras clave: células madre, hidrogeles, plasma, regeneración ósea.doi: http://dx.doi.org/10.7705/biomedica.v34i1.1465 Proliferation and osteogenic differentiation of mesenchymal stem cells in hydrogels of human blood plasmaIntroduction: The use of mesenchymal stem cells in clinical practice has increased considerably in the last decade because they play a supporting role in the processes of tissue repair and regeneration, becoming the main tool of cell therapy for the treatment of diseases functionally affecting bone and cartilage tissue. Objective: To evaluate in vitro the proliferative and osteogenic differentiation ability of mesenchymal stem cells derived from human adipose tissue in a blood plasma hydrogel. Materials and methods: Mesenchymal stem cells were obtained from human adipose tissue explants and characterized by flow cytometry. Their multipotentiality was demonstrated by their ability to differentiate to adipogenic and osteogenic lineages. Cell proliferation and osteogenic differentiation ability of the cells cultured...