Stem cell biology and its therapeutic applications in the setting of spinal cord injury

Bambakidis, Nicholas C.; Butler, John; Horn, Eric M.; Wang, Xukui; Preul, Mark C.; Theodore, Nicholas; Spetzler, Robert F.; Sonntag, Volker K. H.

doi:10.3171/foc/2008/24/3-4/e19

Cited by 27 publications

(15 citation statements)

References 33 publications

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“…There is accelerating interest in developing adult-derived mesenchymal stromal and other stem cells as therapeutic agents for the treatment of graft versus host disease (GVHD), cardiac indications, central nervous system (CNS) injury, and CNS disease pathologies [1][2][3][4][5]. Adult stromal cells have been isolated from multiple tissues and characterized [6].…”

Section: Introductionmentioning

confidence: 99%

Dissection of the Human Multipotent Adult Progenitor Cell Secretome by Proteomic Analysis

Burrows

Hof

Newell

et al. 2013

Stem Cells Translational Medicine

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Multipotent adult progenitor cells (MAPCs) are adult adherent stromal stem cells currently being assessed in acute graft versus host disease clinical trials with demonstrated immunomodulatory capabilities and the potential to ameliorate detrimental autoimmune and inflammation-related processes. Our previous studies documented that MAPCs secrete factors that play a role in regulating T-cell activity. Here we expand our studies using a proteomics approach to characterize and quantify MAPC secretome components secreted over 72 hours in vitro under steady-state conditions and in the presence of the inflammatory triggers interferon-␥ and lipopolysaccharide, or a tolerogenic CD74 ligand, RTL1000. MAPCs differentially responded to each of the tested stimuli, secreting molecules that regulate the biological activity of the extracellular matrix (ECM), including proteins that make up the ECM itself, proteins that regulate its construction/deconstruction, and proteins that serve to attach and detach growth factors from ECM components for redistribution upon appropriate stimulation. MAPCs secreted a wide array of proteases, some detectable in their zymogen forms. MAPCs also secreted protease inhibitors that would regulate protease activity. MAPCs secreted chemokines and cytokines that could provide molecular guidance cues to various cell types, including neutrophils, macrophages, and T cells. In addition, MAPCs secreted factors involved in maintenance of a homeostatic environment, regulating such diverse programs as innate immunity, angiogenesis/angiostasis, targeted delivery of growth factors, and the matrix-metalloprotease cascade. STEM CELLS TRANSLATIONAL MEDICINE 2013;2:745-757

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Section: Introductionmentioning

confidence: 99%

Dissection of the Human Multipotent Adult Progenitor Cell Secretome by Proteomic Analysis

Burrows

Hof

Newell

et al. 2013

Stem Cells Translational Medicine

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show abstract

“…There is substantial interest in developing adult-derived stem cells as therapeutic agents for the treatment of CNS injury and disease (Biernaskie et al, 2007; Bambakidis et al, 2008; Barnabé-Heider and Frisén, 2008). Adult-derived adherent stem cells demonstrate a number of favorable characteristics including genetic stability, extensive expansion capacity, and low immunogenicity profiles that support allogeneic utility (Gnecchi et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Multipotent Adult Progenitor Cells Prevent Macrophage-Mediated Axonal Dieback and Promote Regrowth after Spinal Cord Injury

et al. 2011

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Macrophage-mediated axonal dieback presents an additional challenge to regenerating axons after spinal cord injury. Adult adherent stem cells are known to have immunomodulatory capabilities, but their potential to ameliorate this detrimental inflammation-related process has not been investigated. Using an in vitro model of axonal dieback as well as an adult rat dorsal column crush model of spinal cord injury, we found that multipotent adult progenitor cells (MAPCs) can affect both macrophages and dystrophic neurons simultaneously. MAPCs significantly decrease MMP-9 (matrix metalloproteinase-9) release from macrophages, effectively preventing induction of axonal dieback. MAPCs also induce a shift in macrophages from an M1, or “classically activated” proinflammatory state, to an M2, or “alternatively activated” antiinflammatory state. In addition to these effects on macrophages, MAPCs promote sensory neurite outgrowth, induce sprouting, and further enable axons to overcome the negative effects of macrophages as well as inhibitory proteoglycans in their environment by increasing their intrinsic growth capacity. Our results demonstrate that MAPCs have therapeutic benefits after spinal cord injury and provide specific evidence that adult stem cells exert positive immunomodulatory and neurotrophic influences.

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“…Inflammation in the CNS predominantly involves microglia and macrophages, which are believed to be a significant cause of secondary injury following SCI, but also may contribute to its repair (Batchelor et al 2008;Ahn et al 2006). Inflammatory cells are also associated with delayed neuronal death, demyelination (Beattie 2004) and scar tissue formation (Bambakidis et al 2008). In this study, the number of CD-68 positive cells was less in rostral transplantation rats than seen in caudal transplantation rats.…”

Section: Discussionmentioning

confidence: 91%

Optimal Location and Time for Neural Stem Cell Transplantation into Transected Rat Spinal Cord

Zhang

Wang

2010

Cell Mol Neurobiol

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Implanted neural stem cells (NSC) could improve neurological functions following spinal cord injury (SCI), but the optimal conditions for NSC transplantation are largely unknown, especially in transected spinal cord. This study investigated the effect and fate of NSC engrafted into spinal cords at different locations and time points following T(9) spinal cord transection. Engrafted NSC could survive and migrate in host spinal cords. Significant improvement in hindlimb locomotor functions associated with NSC survival was found in rats receiving NSC transplantation in the spinal cords rostral to the transection site at the subacute stage (7 days post operation), compared with those caudal to the transection site at the acute stage (at the time of injury). At 4 weeks post operation, CD68 immunohistochemical staining confirmed that macrophages were less in rostrally transplanted sites and in subacute groups than seen in caudal and acute transplanted rats. The present findings indicated that NSC transplantation into spinal cords rostral to transection site at the subacute stage is an optimal strategy for engrafted NSC survival and host behavioral improvement. It therefore would be available to the usage of NSC for the treatment of SCI in the future clinic trial.

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Stem cell biology and its therapeutic applications in the setting of spinal cord injury

Cited by 27 publications

References 33 publications

Dissection of the Human Multipotent Adult Progenitor Cell Secretome by Proteomic Analysis

Dissection of the Human Multipotent Adult Progenitor Cell Secretome by Proteomic Analysis

Multipotent Adult Progenitor Cells Prevent Macrophage-Mediated Axonal Dieback and Promote Regrowth after Spinal Cord Injury

Optimal Location and Time for Neural Stem Cell Transplantation into Transected Rat Spinal Cord

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