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A safety study on intrathecal delivery of autologous mesenchymal stromal cells in rabbits directly supporting P hase I human trials
Author(s) -
Chen Bingkun K.,
Staff Nathan P.,
Knight Andrew M.,
Nesbitt Jarred J.,
Butler Greg W.,
Padley Douglas J.,
Parisi Joseph E.,
Dietz Allan B.,
Windebank Anthony J.
Publication year - 2015
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.12938
Subject(s) - medicine , mesenchymal stem cell , cerebrospinal fluid , foramen magnum , atrophy , adipose tissue , intrathecal , clinical trial , umbilical cord , stromal cell , multiple sclerosis , pathology , surgery , immunology
Background There are no effective treatments that slow the progression of neurodegenerative diseases. A major challenge of treatment in neurodegenerative diseases is appropriate delivery of pharmaceuticals into the cerebrospinal fluid ( CSF ) of affected individuals. Mesenchymal stromal cells ( MSC s—either naïve or modified) are a promising therapy in neurodegenerative diseases and may be delivered directly into the CSF where they can reside for months. In this preclinical study, we evaluated the safety of intrathecal autologous MSC s in a rabbit model. Study Design and Methods Autologous adipose‐derived MSC s (or artificial CSF ) were delivered intrathecally, either with single or with repeated injections into the foramen magnum of healthy rabbits and monitored for 4 and 12 weeks, respectively. Results Rabbits tolerated injections well and no definitive MSC ‐related side effects were observed apart from three rabbits that had delayed death secondary to traumatic foramen magnum puncture. Functional assessments and body weights were equivalent between groups. Gross pathology and histology did not reveal any abnormalities or tumor growth. Complete blood count data were normal and there were no differences in CSF interleukin‐6 levels in all groups tested. Conclusion Our data suggest that intrathecal delivery of autologous MSC s is safe in a rabbit model. Data from this study have supported two successful investigational new drug applications to the F ood and D rug A dministration, resulting in the initiation of two clinical trials using autologous MSC s in amyotrophic lateral sclerosis and multiple system atrophy.