Human Mesenchymal Cells from Adipose Tissue Deposit Laminin and Promote Regeneration of Injured Spinal Cord in Rats

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.

Heterotypic control of basement membrane dynamics during branching morphogenesis

“…Ultimately, scaffolds that best support dynamic homotypic and heterotypic cell interactions and encourage the cells to deposit and remodel their own extracellular matrices and basement membranes may be required to engineer functional and sustainable organs. Eventual development of tissue-engineered constructs capable of long-term maintenance of homeostasis will require recapitulation of a niche for renewing progenitor cell populations (Dziasko et al, 2014; Fujiwara et al, 2011; Marthiens et al, 2010; Menezes et al, 2014). In regenerating tissues, similar considerations for strategies to promote recapitulation of the complex developmental programs and restoration of the microenvironment and progenitor cell niches are required.…”

Stem cells for spine surgery

“…Several different studies in rat models found that MSCs induce nerve regeneration, modulate the production of inflammatory cytokines such as TNF-α and IL-6 and reduce myeloperoxidase activity [101][102][103][104][105] . Menezes et al [106] hypothesized that laminin may play a pivotal role in neuron and axon preservation and regeneration after finding deposits of the glycoprotein on the lesion site …”

“…Spinal cord injury (SCI) results from traumatic damage to the spinal cord which may have devastating consequences in a rat SCI model [106] . All of these studies reported that transplanted MSCs operate mainly through the creation of a favorable microenvironment by means of the secretion of a variety of neurotrophic factors [107][108][109][110][111] .…”

Efficacy of human HC016 cell transplants on neuroprotection and functional recovery in a rat model of acute spinal cord injury

“…Moreover, we grafted the cells 48 hr after producing the SCI, with the aim of contributing to reduce the secondary damage responsible for most of the neural tissue loss and thus functional sequelae. However, such an early administration of a cell therapy has as main limitation the hostile environment elicited in the acutely injured tissue after SCI and thus the survival of the grafted cells (Arboleda et al, ; Menezes et al, ).…”

“…Among cell therapies, mesenchymal stem cell (MSC) transplantation is an attractive and promising approach for treating SCI favoured by its excellent safety profile and efficacy potential, as extensively reported in preclinical models and clinical trials of acute, subacute, and chronic SCI (Dasari, Veeravalli, & Dinh, ; Qu & Zhang, ; Shende & Subedi, ; Vawda & Fehlings, ). In particular, adipose MSCs (AMSCs) are easily obtained and have excellent expansion capacities, as well as a unique immunomodulatory and paracrine competence able to modulate many of the detrimental effects elicited after acute SCI (Mazini, Rochette, Amine, & Malka, ; Menezes et al, ; Takahashi et al, ). These effects together with a proven preclinical efficacy and safety profile have paved the way for the clinical assessment of AMSCs in a variety of trials (Bajek et al, ; Hur et al, ; Jin et al, ).…”