Assessment of biodistribution using mesenchymal stromal cells: Algorithm for study design and challenges in detection methodologies
Por:
Reyes, B, Coca, MI, Codinach, M, Lopez-Lucas, MD, del Mazo-Barbara, A, Caminal, M, Oliver-Vila, I, Cabanas, V, Lope-Piedrafita, S, Garcia-Lopez, J, Moraleda, JM, Fontecha, CG, Vives, J
Publicada:
1 sep 2017
Resumen:
Background aims. Biodistribution of candidate cell-based therapeutics is a critical safety concern that must be addressed in the preclinical development program. We aimed to design a decision tree based on a series of studies included in actual dossiers approved by competent regulatory authorities, noting that the design, execution and interpretation of pharmacokinetics studies using this type of therapy is not straightforward and presents a challenge for both developers and regulators. Methods. Eight studies were evaluated for the definition of a decision tree, in which mesenchymal stromal cells (MSCs) were administered to mouse, rat and sheep models using diverse routes (local or systemic), cell labeling (chemical or genetic) and detection methodologies (polymerase chain reaction [PCR], immunohistochemistry [IHC], fluorescence bioimaging, and magnetic resonance imaging [MRI]). Moreover, labeling and detection methodologies were compared in terms of cost, throughput, speed, sensitivity and specificity. Results. A decision tree was defined based on the model chosen: (i) small immunodeficient animals receiving heterologous MSC products for assessing biodistribution and other safety aspects and (ii) large animals receiving homologous labeled products; this contributed to gathering data not only on biodistribution but also on pharmacodynamics. PCR emerged as the most convenient technique despite the loss of spatial information on cell distribution that can be further assessed by IHC. Discussion. This work contributes to the standardization in the design of biodistribution studies by improving methods for accurate assessment of safety. The evaluation of different animal models and screening of target organs through a combination of techniques is a cost-effective and timely strategy.
Filiaciones:
Reyes, B:
Banc Sang & Teixits, Serv Terapia Cellular, Edifici Dr Frederic Duran I Jorda, Barcelona 08005, Spain
Coca, MI:
Banc Sang & Teixits, Serv Terapia Cellular, Edifici Dr Frederic Duran I Jorda, Barcelona 08005, Spain
Codinach, M:
Banc Sang & Teixits, Serv Terapia Cellular, Edifici Dr Frederic Duran I Jorda, Barcelona 08005, Spain
Lopez-Lucas, MD:
Univ Murcia, IMIB, Unidad Terapia Celular & Trasplante Hematopoyet, Hosp Clin Univ Virgen Arrixaca, Murcia, Spain
del Mazo-Barbara, A:
Banc Sang & Teixits, Serv Terapia Cellular, Edifici Dr Frederic Duran I Jorda, Barcelona 08005, Spain
Caminal, M:
Banc Sang & Teixits, Serv Terapia Cellular, Edifici Dr Frederic Duran I Jorda, Barcelona 08005, Spain
Oliver-Vila, I:
Banc Sang & Teixits, Serv Terapia Cellular, Edifici Dr Frederic Duran I Jorda, Barcelona 08005, Spain
Cabanas, V:
Univ Murcia, IMIB, Unidad Terapia Celular & Trasplante Hematopoyet, Hosp Clin Univ Virgen Arrixaca, Murcia, Spain
Lope-Piedrafita, S:
Univ Autonoma Barcelona, Ser Ressonancia Magnet Nucl, Cerdanyola Del Valles, Spain
Univ Autonoma Barcelona, CIBERBBN, Cerdanyola Del Valles, Spain
Garcia-Lopez, J:
Banc Sang & Teixits, Serv Terapia Cellular, Edifici Dr Frederic Duran I Jorda, Barcelona 08005, Spain
Univ Autonoma Barcelona, Chair Transfus Med & Cellular & Tissue Therapies, Bellaterra, Cerdanyola Del, Spain
Moraleda, JM:
Univ Murcia, IMIB, Unidad Terapia Celular & Trasplante Hematopoyet, Hosp Clin Univ Virgen Arrixaca, Murcia, Spain
Fontecha, CG:
Univ Autonoma Barcelona, VHIR, Reconstruct Surg Locomotor Syst, Barcelona, Spain
Vives, J:
Banc Sang & Teixits, Serv Terapia Cellular, Edifici Dr Frederic Duran I Jorda, Barcelona 08005, Spain
Univ Autonoma Barcelona, Dept Med, Bellaterra, Cerdanyola Del, Spain
Univ Autonoma Barcelona, VHIR, Tissue Engn Grp, Barcelona, Spain
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