Significant clinical, neuropathological and behavioural recovery from acute spinal cord trauma by transplantation of a well-defined somatic stem cell from human umbilical cord blood

Abstract

Stem cell therapy is a potential treatment for spinal cord injury and different stem cell types have been grafted into animal models and humans suffering from spinal trauma. Due to inconsistent results, it is still an important and clinically relevant question which stem cell type will prove to be therapeutically effective. Thus far, stem cells of human sources grafted into spinal cord mostly included barely defined heterogeneous mesenchymal stem cell populations derived from bone marrow or umbilical cord blood. Here, we have transplanted a well-defined unrestricted somatic stem cell isolated from human umbilical cord blood into an acute traumatic spinal cord injury of adult immune suppressed rat. Grafting of unrestricted somatic stem cells into the vicinity of a dorsal hemisection injury at thoracic level eight resulted in hepatocyte growth factor-directed migration and accumulation within the lesion area, reduction in lesion size and augmented tissue sparing, enhanced axon regrowth and significant functional locomotor improvement as revealed by three behavioural tasks (open field Basso-Beattie-Bresnahan locomotor score, horizontal ladder walking test and CatWalk gait analysis). To accomplish the beneficial effects, neither neural differentiation nor long-lasting persistence of the grafted human stem cells appears to be required. The secretion of neurite outgrowth-promoting factors in vitro further suggests a paracrine function of unrestricted somatic stem cells in spinal cord injury. Given the highly supportive functional characteristics in spinal cord injury, production in virtually unlimited quantities at GMP grade and lack of ethical concerns, unrestricted somatic stem cells appear to be a highly suitable human stem cell source for clinical application in central nervous system injuries.

Neural Fate of Mesenchymal Stem Cells and Neural Crest Stem Cells: Which Ways to Get Neurons for Cell Therapy Purpose?

“…Significant enhancement of functional locomotor abilities was observed by Schira et al after transplantation of unrestricted UCB-MSCs into the surrounding area of a hemisection injury, accompanied by cell accumulation near the lesion, reduction in its size and enhanced axon regrowth [107]. This study gives an example of what can be observed using naïve stem cells in cell therapy, without any pre-differentiation.…”

Characterization of Regenerative Phenotype of Unrestricted Somatic Stem Cells (USSC) from Human Umbilical Cord Blood (hUCB) by Functional Secretome Analysis

“…Preparation and Cultivation of Primary Rat Cortical Neurons-To test potential neurite growth promoting factors found in USSC secretome, primary cortical neurons were prepared from E15 Wistar rats as described before (11,35) and subsequently incubated with serumfree conditioned medium derived from USSC. N2 medium as well as conditioned medium derived from primary cortical astrocytes prepared from p0-p1 Wistar rats (11,36) served as negative and positive controls, respectively.…”

“…As USSC can be easily isolated at GMP (good manufacturing practice) grade (10) and expanded on a clinical scale, USSC are a promising tool for transplantation studies. In a recent study, we have demonstrated that after transplantation into the acute injured rat spinal cord, USSC induce significant axon regrowth into the lesion side and effectively improve long-term functional locomotor recovery (11). Moreover, USSC transplantation promotes tissue sparing, which might contribute to the locomotor improvement.…”

Rescuing the neonatal brain from hypoxic injury with autologous cord blood

“…In addition to HSCs, non-hematopoietic stem cell populations exist in CB, including, but not limited to, MSCs and more primitive stem cell populations with multi-lineage differentiation properties, that is, unrestricted somatic stem cells, multi-lineage progenitor cells, embryonic-like stem cells and very small embryonic-like stem cells that have respectively been shown to differentiate into neural cells. 14,17,[61][62][63][64][65] MSCs, which can also be isolated from BM and other sources, have been demonstrated to exert neuro-protection in HIE animal models. [66][67][68][69][70] Cell lines with NSC properties have been established from HUCB following immune-depletion of the CD34-positive cells from CB and spontaneous aggregation and differentiation with stimulation by epithelial growth factor.…”

“…Stem cells from different sources, such as neural stem/progenitor cells derived from either fetal tissue or embryonic stem-induced pluripotent stem cells, MSCs, human umbilical cord blood (HUCB)-derived stem cells or HUCB mononuclear cells, have been utilized in several animal models of neurological diseases. [10][11][12][13][14] Cord blood (CB) has been clinically proven to be an effective stem cell source to prevent neurological deterioration in patients with inborn metabolic disorders, that is, Krabbe's disease and Hurler's syndrome. 15,16 A significant advantage of HUCB cells over other sources of stem cells in tissue regeneration is the ready availability of HUCB.…”