Abstract

Cell therapy is a promising strategy to pursue the unmet need for treatment of spinal cord injury (SCI). Although several studies have shown that adult mesenchymal cells contribute to improve the outcomes of SCI, a descripton of the pro-regenerative events triggered by these cells is still lacking. Here we investigated the regenerative properties of human adipose tissue derived stromal cells (hADSCs) in a rat model of spinal cord compression. Cells were delivered directly into the spinal parenchyma immediately after injury. Human ADSCs promoted functional recovery, tissue preservation, and axonal regeneration. Analysis of the cord tissue showed an abundant deposition of laminin of human origin at the lesion site and spinal midline; the appearance of cell clusters composed of neural precursors in the areas of laminin deposition, and the appearance of blood vessels with separated basement membranes along the spinal axis. These effects were also observed after injection of hADSCs into non-injured spinal cord. Considering that laminin is a well-known inducer of axonal growth, as well a component of the extracellular matrix associated to neural progenitors, we propose that it can be the paracrine factor mediating the pro-regenerative effects of hADSCs in spinal cord injury.

Highlights

  • Traumatic brain and spinal cord injuries affect individuals of all ages, causing various degrees of disability [1,2]

  • In order to evaluate if human subcutaneous adipose-derived stromal cells (ADSCs) would improve the functional outcome after compressive spinal cord injury (SCI), we compared the open field locomotion (BBB scores) of animals receiving cells or culture medium (DMEM)

  • Animals treated with human adipose tissue derived stromal cells (hADSCs) exhibited superior scores from the first evaluation, whereas such superiority became statistically significant from the fifth week on

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Summary

Introduction

Traumatic brain and spinal cord injuries affect individuals of all ages, causing various degrees of disability [1,2]. The primary source of progenitor cells is the bone marrow, where at least the hematopoietic stem cell and a population of mesenchymal stromal/stem cells co-exist (MSC) [10] Both cell types have been used to treat experimental spinal cord injury (SCI) in animals, as well as injured human patients [11]. A growing number of studies have reported the effects of MSCs in promoting functional improvement, tissue sparing, and axonal growth after spine cord injury [13,14,15,16,17,18,19,20,21,22,23]. A recent study compared the effectiveness of hADSCs with that of human bone marrow stromal cells in a model of section injury in immunossupressed rats and reported the superior regenerative effect of hADSCs [29]. PLOS ONE | www.plosone.org hADSCs Secrete Laminin and Promote Regeneration after SCI

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