A Phase I Dose-Escalation Clinical Trial to Assess the Safety and Efficacy of Umbilical Cord-Derived Mesenchymal Stromal Cells in Knee Osteoarthritis.

Osteoarthritis (OA) is the most common degenerative joint disease. Mesenchymal stromal cells (MSC) are promising cell-based therapy for OA. However, there is still a need for additional randomized, dose-dependent studies to determine the optimal dose and tissue source of MSC for improved clinical outcomes. Here, we performed a dose-dependant evaluation of umbilical cord (UC)-derived MSC (Celllistem) in a murine model and in knee OA patients. For the preclinical study, a classical dose (200.000 cells) and a lower dose (50.000 cells) of Cellistem were intra-articularly injected into the mice knee joints. The results showed a dose efficacy response effect of Cellistem associated with a decreased inflammatory and degenerative response according to the Pritzker OARSI score. Following the same approach, the dose-escalation phase I clinical trial design included 3 sequential cohorts: low-dose group (2 × 106 cells), medium-dose group (20 × 106), and high-dose group (80 × 106). All the doses were safe, and no serious adverse events were reported. Nonetheless, 100% of the patients injected with the high-dose experienced injection-related swelling in the knee joint. According to WOMAC total outcomes, patients treated with all doses reported significant improvements in pain and function compared with baseline after 3 and 6 months. However, the improvements were higher in patients treated with both medium and low dose as compared to high dose. Therefore, our data demonstrate that the intra-articular injection of different doses of Cellistem is both safe and efficient, making it an interesting therapeutic alternative to treat mild and symptomatic knee OA patients. Trial registration ClinicalTrials.gov NCT03810521.

Umbilical Cord-Derived Mesenchymal Stromal Cells (MSCs) for Knee Osteoarthritis: Repeated MSC Dosing Is Superior to a Single MSC Dose and to Hyaluronic Acid in a Controlled Randomized Phase I/II Trial.

Knee osteoarthritis (OA) is a leading cause of pain and disability. Although conventional treatments show modest benefits, pilot and phase I/II trials with bone marrow (BM) and adipose-derived (AD) mesenchymal stromal cells (MSCs) point to the feasibility, safety, and occurrence of clinical and structural improvement in focal or diffuse disease. This study aimed to assess the safety and efficacy of the intra-articular injection of single or repeated umbilical cord-derived (UC) MSCs in knee OA. UC-MSCs were cultured in an International Organization for Standardization 9001:2015 certified Good Manufacturing Practice-type Laboratory. Patients with symptomatic knee OA were randomized to receive hyaluronic acid at baseline and 6 months (HA, n = 8), single-dose (20 × 106 ) UC-MSC at baseline (MSC-1, n = 9), or repeated UC-MSC doses at baseline and 6 months (20 × 106 × 2; MSC-2, n = 9). Clinical scores and magnetic resonance images (MRIs) were assessed throughout the 12 months follow-up. No severe adverse events were reported. Only MSC-treated patients experienced significant pain and function improvements from baseline (p = .001). At 12 months, Western Ontario and Mc Master Universities Arthritis Index (WOMAC-A; pain subscale) reached significantly lower levels of pain in the MSC-2-treated group (1.1 ± 1.3) as compared with the HA group (4.3 ± 3.5; p = .04). Pain Visual Analog scale was significantly lower in the MSC-2 group versus the HA group (2.4 ± 2.1 vs. 22.1 ± 9.8, p = .03) at 12 months. For total WOMAC, MSC-2 had lower scores than HA at 12 months (4.2 ± 3.9 vs. 15.2 ± 11, p = .05). No differences in MRI scores were detected. In a phase I/II trial (NCT02580695), repeated UC-MSC treatment is safe and superior to active comparator in knee OA at 1-year follow-up. Stem Cells Translational Medicine 2019;8:215&224.

Factores sociales en la vivencia del cuerp de mujeres con peso normal y con obesidad: rol de la madre, el padre y la pareja / Social factors that affect the corporal experience in normal weight and obse women: the mother's role, the father and the couple

El objetivo de este estudio fue describir y comparar la influencia de factores sociales, específicamente de vínculos cercanos (madre, padre y pareja), sobre la vivencia del cuerpo en mujeres jóvenes con peso normal y con obesidad. Se realizó una investigación exploratoria cualitativa y se analizaron los datos a través de codificación abierta, basada en la Teoría Fundamentada. La muestra estuvo conformada por ocho mujeres, cuatro con obesidad mórbida y cuatro normopeso, entre 20 y 25 años. Los resultados confirman que la insatisfacción corporal está presente en todas las participantes independiente de su peso corporal. Las personas cercanas ejercen presión por la delgadez, la madre estaría más centrada en lo estético, mientras el padre expresaría mayor preocupación por la salud. Las participantes se muestran vulnerables a los mensajes contradictorios de la pareja, generando inseguridad. Sin embargo, la presión de los vínculos cercanos no sería suficiente para generar cambios de hábitos. Se observa ambivalencia entre la valoración de un cuerpo delgado y otro curvilíneo, ideales que se superponen y generan malestar.

The objective of this study was to describe the influence of social factors, specifically close affective bonds (mother, father and couple), on body experience in young women with obesity and normal weight. A qualitative exploratory research was carried out and data were analyzed with Grounded Theory. A sample of eight women between 20 and 25 years old participated, four of them with morbid obesity and four with normal weight. The results confirm that body dissatisfaction is present in all the participants, which is associated with the pressure to be thin exerted by the people close to them. Mothers are more centered on the aesthetic, while fathers seem to have more concern about health. Participants are vulnerable to the couple's conflicting messages, generating insecurity. However, the pressure of the environment does not seem to be enough to change the habits. Ambivalence is observed between the appreciation of a thin body and a curvilinear one at the same time, ideals that overlap and generate discomfort.

[EARLY MOTHER-CHILD BONDING FACTORS ASSOCIATED WITH CHILDREN OBESITY]. / FACTORES DEL VÍNCULO TEMPRANO MADRE-HIJO ASOCIADOS A LA OBESIDAD INFANTIL.

The aim of this study is to describe the experience of a group of mothers with obese children, regarding how early bond affects the relationship that both have with food and this, in turn, impacts on childhood obesity. The present study has a qualitative, exploratory and descriptive design. The sample consists of five chilean women between 22 and 39 years old, with obese children between 2 and 4 years old. In-depth interviews were carried out and open coding strategy was used as method of analysis. Results show a tendency of mothers to establish insecure attachment relations, difficulties of tuning and expression of affection, and a predominance of a permissive parenting style around food. This has important implications for prevention and treatment of obesity, focusing on the attachment bond between mother and child.

El objetivo del presente trabajo es describir las vivencias de un grupo de madres con hijos obesos, respecto a cómo el vínculo temprano madre-hijo afecta a la relación que ambos tienen con la alimentación y cómo esto, a su vez, incide en la obesidad del niño. Estudio cualitativo, exploratorio, de carácter descriptivo. La muestra está constituida por cinco mujeres chilenas entre 22 y 39 años, con hijos obesos entre 2 y 4 años. Se realizaron entrevistas en profundidad y se usó la codificación abierta como técnica de análisis. Los resultados muestran una tendencia de las madres a establecer relaciones de apego inseguro, dificultades de sintonización y expresión afectiva, y predominio de un estilo de crianza permisivo en torno a la comida. Esto tiene importantes implicaciones para la prevención y tratamiento de la obesidad desde el punto de vista de las pautas vinculares madre-hijo.