Earlier research primarily attributed the effects of mesenchymal stem cell (MSC) therapies to their capacity for local engrafting and differentiating into multiple tissue types. However, recent studies have revealed that implanted cells do not survive for long, and that the benefits of MSC therapy could be due to the vast array of bioactive factors they produce, which play an important role in the regulation of key biologic processes. Secretome derivatives, such as conditioned media or exosomes, may present considerable advantages over cells for manufacturing, storage, handling, product shelf life and their potential as a ready-to-go biologic product. Nevertheless, regulatory requirements for manufacturing and quality control will be necessary to establish the safety and efficacy profile of these products. Among MSCs, human uterine cervical stem cells (hUCESCs) may be a good candidate for obtaining secretome-derived products. hUCESCs are obtained by Pap cervical smear, which is a less invasive and painful method than those used for obtaining other MSCs (for example, from bone marrow or adipose tissue). Moreover, due to easy isolation and a high proliferative rate, it is possible to obtain large amounts of hUCESCs or secretome-derived products for research and clinical use.

https://www.mdpi.com/1422-0067/18/9/1852/pdf

Mesenchymal Stem Cell Secretome: Toward Cell-Free Therapeutic Strategies in Regenerative Medicine

The matrix metalloproteinases and related A disintegrin and metalloproteinase enzymes are implicated in various diseases of the nervous system. However, metalloproteinases are increasingly being recognized as having beneficial roles during nervous system development and following injury. This review discusses general principles that govern the expression of metalloproteinases in the nervous system and their detrimental outcomes. It then focuses on the roles of metalloproteinases and their mechanisms in regulating neurogenesis, myelin formation and axonal growth. It is clear that metalloproteinases are important determinants in enabling recovery from injury to the nervous system.

http://www.vweeyong.com/pdf/05/Yong,%20Nature%20Rev%20Neurosci%206,%20931,%202005.pdf

Metalloproteinases: Mediators of Pathology and Regeneration in the CNS

Regenerative medicine, the most recent and emerging branch of medical science, deals with functional restoration of tissues or organs for the patient suffering from severe injuries or chronic disease. The spectacular progress in the field of stem cell research has laid the foundation for cell based therapies of disease which cannot be cured by conventional medicines. The indefinite self-renewal and potential to differentiate into other types of cells represent stem cells as frontiers of regenerative medicine. The transdifferentiating potential of stem cells varies with source and according to that regenerative applications also change. Advancements in gene editing and tissue engineering technology have endorsed the ex vivo remodelling of stem cells grown into 3D organoids and tissue structures for personalized applications. This review outlines the most recent advancement in transplantation and tissue engineering technologies of ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs in regenerative medicine. Additionally, this review also discusses stem cells regenerative application in wildlife conservation.

/pdf/stem-cells-applications-in-regenerative-medicine-and-disease-8k5gj3p888.pdf

Stem Cells Applications in Regenerative Medicine and Disease Therapeutics

Spinal cord injury results in acute as well as progressive secondary destruction of local and distant nervous tissue through a number of degenerative mechanisms. Spinal cord injury also initiates a number of endogenous neuroprotective and regenerative responses. Understanding of these mechanisms might identify potential targets for treatments after spinal cord injury in humans. Here, we first discuss recent developments in our understanding of the immediate traumatic and subsequent secondary degeneration of local tissue and long projecting pathways in animal models. These include the inflammatory and vascular responses during the acute phase, as well as cell death, demyelination and scar formation in the subacute and chronic phases. Secondly, we discuss the spontaneous axonal regeneration of injured and plasticity of uninjured systems, and other repair-related responses in animals, including the upregulation of regeneration-associated genes in some neurons, increases in neurotrophic factors in the spinal cord and remyelination by oligodendrocyte precursors and invading Schwann cells. Lastly, we comment on the still limited understanding of the neuropathology in humans, which is largely similar to that in rodents. However, there also are potentially important differences, including the reduced glial scarring, inflammation and demyelination, the increased Schwannosis and the protracted Wallerian degeneration in humans. The validity of current rodent models for human spinal cord injury is also discussed. The emphasis of this review is on the literature from 2002 to early 2005.

Degenerative and spontaneous regenerative processes after spinal cord injury.

Stem cells: their source, potency and use in regenerative therapies with focus on adipose-derived stem cells - a review.

We have investigated and compared the neurotrophic activity of human dental pulp stem cells (hDPSC), human bone marrow-derived mesenchymal stem cells (hBMSC) and human adipose-derived stem cells (hAMSC) on axotomised adult rat retinal ganglion cells (RGC) in vitro in order to evaluate their therapeutic potential for neurodegenerative conditions of RGC. Using the transwell system, RGC survival and length/number of neurites were quantified in coculture with stem cells in the presence or absence of specific Fc-receptor inhibitors to determine the role of NGF, BDNF, NT-3, VEGF, GDNF, PDGF-AA and PDGF-AB/BB in stem cell-mediated RGC neuroprotection and neuritogenesis. Conditioned media, collected from cultured hDPSC/hBMSC/hAMSC, were assayed for the secreted growth factors detailed above using ELISA. PCR array determined the hDPSC, hBMSC and hAMSC expression of genes encoding 84 growth factors and receptors. The results demonstrated that hDPSC promoted significantly more neuroprotection and neuritogenesis of axotomised RGC than either hBMSC or hAMSC, an effect that was neutralized after the addition of specific Fc-receptor inhibitors. hDPSC secreted greater levels of various growth factors including NGF, BDNF and VEGF compared with hBMSC/hAMSC. The PCR array confirmed these findings and identified VGF as a novel potentially therapeutic hDPSC-derived neurotrophic factor (NTF) with significant RGC neuroprotective properties after coculture with axotomised RGC. In conclusion, hDPSC promoted significant multi-factorial paracrine-mediated RGC survival and neurite outgrowth and may be considered a potent and advantageous cell therapy for retinal nerve repair.

/pdf/paracrine-mediated-neuroprotection-and-neuritogenesis-of-mg5x9ndtzo.pdf

Paracrine-Mediated Neuroprotection and Neuritogenesis of Axotomised Retinal Ganglion Cells by Human Dental Pulp Stem Cells: Comparison with Human Bone Marrow and Adipose-Derived Mesenchymal Stem Cells

Purpose.: To investigate the potential therapeutic benefit of intravitreally implanted dental pulp stem cells (DPSCs) on axotomized adult rat retinal ganglion cells (RGCs) using in vitro and in vivo neural injury models.

Methods.: Conditioned media collected from cultured rat DPSCs and bone marrow–derived mesenchymal stem cells (BMSCs) were assayed for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) secretion using ELISA. DPSCs or BMSCs were cocultured with retinal cells, with or without Fc-TrK inhibitors, in a Transwell system, and the number of surviving βIII-tubulin+ retinal cells and length/number of βIII-tubulin+ neurites were quantified. For the in vivo study, DPSCs or BMSCs were transplanted into the vitreous body of the eye after a surgically induced optic nerve crush injury. At 7, 14, and 21 days postlesion (dpl), optical coherence tomography (OCT) was used to measure the retinal nerve fiber layer thickness as a measure of axonal atrophy. At 21 dpl, numbers of Brn-3a+ RGCs in parasagittal retinal sections and growth-associated protein-43+ axons in longitudinal optic nerve sections were quantified as measures of RGC survival and axon regeneration, respectively.

Results.: Both DPSCs and BMSCs secreted NGF, BDNF, and NT-3, with DPSCs secreting significantly higher titers of NGF and BDNF than BMSCs. DPSCs, and to a lesser extent BMSCs, promoted statistically significant survival and neuritogenesis/axogenesis of βIII-tubulin+ retinal cells in vitro and in vivo where the effects were abolished after TrK receptor blockade. Conclusions.: Intravitreal transplants of DPSCs promoted significant neurotrophin-mediated RGC survival and axon regeneration after optic nerve injury.

/pdf/intravitreally-transplanted-dental-pulp-stem-cells-promote-2q7h9wx68s.pdf

Intravitreally transplanted dental pulp stem cells promote neuroprotection and axon regeneration of retinal ganglion cells after optic nerve injury.

https://research.birmingham.ac.uk/portal/files/18425341/Mead_et_al_Stem_Cell_Res_14_243_257_2015.pdf

Stem cell treatment of degenerative eye disease

Lecture recordings are increasingly used to supplement lecture attendance within higher education, but their impact on student learning remains unclear. Here we describe a study to evaluate student use of lecture recordings and quantify their impact on academic performance. Questionnaire responses and online monitoring of student's access to recordings indicate that ~75% students use this material, the majority in a targeted manner. In contrast, a small subset of students (~5%) are highly dependent on recordings downloading every lecture, and viewing the material for long periods, such that this represents a large proportion of their independent study. This 'high user' group is atypical, as it contains a high proportion of dyslexic and Non-English Speaking Background students. Despite high usage, lecture recordings do not have a significant impact on academic performance, either across the cohort or with students that use the recordings. Overall, this approach appears to be beneficial, but may reduce lecture attendance and encourage surface learning approaches in a minority of students.

Wendy Leadbeater

Papers

Paracrine-Mediated Neuroprotection and Neuritogenesis of Axotomised Retinal Ganglion Cells by Human Dental Pulp Stem Cells: Comparison with Human Bone Marrow and Adipose-Derived Mesenchymal Stem Cells

Intravitreally transplanted dental pulp stem cells promote neuroprotection and axon regeneration of retinal ganglion cells after optic nerve injury.

Stem cell treatment of degenerative eye disease

Evaluating the use and impact of lecture recording in undergraduates: Evidence for distinct approaches by different groups of students

Matrix metalloproteases: degradation of the inhibitory environment of the transected optic nerve and the scar by regenerating axons