Safety and Biodistribution of Human Bone Marrow-Derived Mesenchymal Stromal Cells Injected Intrathecally in Non-Obese Diabetic Severe Combined Immunodefi ciency Mice: Preclinical Study

BACKGROUND: Mesenchymal stromal cells (MSCs) have potent immunomodulatory and neuroprotective properties, and have been tested in neurodegenerative diseases resulting in meaningful clinical improvements. Regulatory guidelines specify the need to perform preclinical studies prior any clinical trial, including biodistribution assays and tumourigenesis exclusion. We conducted a preclinical study of human bone marrow MSCs (hBM-MSCs) injected by intrathecal route in Non-Obese Diabetic Severe Combined Immunodeficiency mice, to explore cellular biodistribution and toxicity as a privileged administration method for cell therapy in Friedreich's Ataxia. METHODS: For this purpose, 3 × 10⁵ cells were injected by intrathecal route in 12 animals (experimental group) and the same volume of culture media in 6 animals (control group). Blood samples were collected at 24 h (n = 9) or 4 months (n = 9) to assess toxicity, and nine organs were harvested for histology and safety studies. Genomic DNA was isolated from all tissues, and mouse GAPDH and human β2M and β-actin genes were amplified by qPCR to analyze hBM-MSCs biodistribution. RESULTS: There were no deaths nor acute or chronic toxicity. Hematology, biochemistry and body weight were in the range of normal values in all groups. At 24 h hBM-MSCs were detected in 4/6 spinal cords and 1/6 hearts, and at 4 months in 3/6 hearts and 1/6 brains of transplanted mice. No tumours were found. CONCLUSION: This study demonstrated that intrathecal injection of hBM-MSCs is safe, non toxic and do not produce tumors. These results provide further evidence that hBM-MSCs might be used in a clinical trial in patients with FRDA.

Las tareas de la psicología actual en el campo de las ciencias sociales (una aproximación desde el enfoque de la complejidad) / The tasks of contemporary psychology between social sciences (an approach from the complexity standpoint)

En el presente trabajo se aborda el problema de la construcción transdisciplinaria en las ciencias sociales y las tareas de la psicología ante tal exigencia. Se parte tanto de las demandas epistemológicas propias del desarrollo de la teoría científica como de las necesidades de la práctica. La psicología juega un papel importante en tal obra como una ciencia integradora de lo biológico y lo social. El análisis se realiza desde una perspectiva dialéctica acerca del sujeto dentro de su situación social del desarrollo - principio clave de la psicología vygotskiana. El enfoque de la complejidad aporta criterios fundamentales para conseguir tal visión integradora.

Perioperative Anticoagulation in Patients with Mechanical Heart Valves Undergoing Elective Surgery: Results of a Survey Conducted among Korean Physicians

The optimal perioperative anticoagulation management in patients on warfarin therapy is poorly defined due to the lack of randomized trials. Because guidelines are heterogeneous, it was hypothesized that "treatment strategies are not uniform in clinical practice". Between February 2003 and May 2003, a questionnaire with 4 different clinical scenarios was distributed to physicians by e-mail, or direct contact was made by a survey monitor. Two scenarios described the cases of patients with a mechanical heart valve (MHV) in the mitral position, with additional risk factors for a systemic embolism; one undergoing major (scenario 1) and the other minor surgery (scenario 3). Two scenarios described patients with an aortic MHV; one undergoing major (scenario 2) and the other minor (scenario 4) surgery. Different preoperative and postoperative management options were offered. The treatment options for all scenarios were the same. Of the 90 questionnaires distributed, 52 (57.8%) were returned. Hospitalization for full-dose intravenous unfractionated heparin (IV UH) was the most commonly selected strategy in the preoperative phase for scenarios 1 (59%), 2 (42%) and 3 (44%). In scenario 4, 34% chose IV UH. Outpatient, full- dose, subcutaneous UH or low-molecular-weight heparin (LMWH) was the most selected option in the postoperative phase for all scenarios, with the exception of number 4 (52.9% in scenario 1, 34% in scenario 2, 32%, in scenario 3 and 28% in scenario 4). Even among expert clinicians, the management of perioperative anticoagulation is heterogeneous. In particular, the definition of risk categories and the optimal intensity of antithrombotic drugs need to be defined by well-designed prospective studies.