The reduction in immunogenicity of neurotrophin overexpressing stem cells after intra-striatal transplantation by encapsulation in an in situ gelling collagen hydrogel

Hoban, Deirdre B.; Newland, Ben; Moloney, Teresa C.; Howard, Linda; Pandit, Abhay; Dowd, Eilís

doi:10.1016/j.biomaterials.2013.08.073

Cited by 73 publications

(97 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This confirmed successful GDNF transduction of the MSCs prior to transplantation in vivo. We also demonstrated that GDNF was released from GDNFMSCs after implantation into the striatum (Fig 1 B) and, in line with our previous reports (Moloney et al, 2010b;Hoban et al, 2013b), that its release declined over time due to poor cell survival.…”

Section: Gdnf-transduced Mscs Secrete Gdnf In Vitrosupporting

confidence: 91%

GDNF-secreting mesenchymal stem cells provide localized neuroprotection in an inflammation-driven rat model of Parkinson’s disease

2015

View full text Add to dashboard Cite

Section: Gdnf-transduced Mscs Secrete Gdnf In Vitrosupporting

confidence: 91%

GDNF-secreting mesenchymal stem cells provide localized neuroprotection in an inflammation-driven rat model of Parkinson’s disease

2015

View full text Add to dashboard Cite

“…While we have shown that virally manipulated, GDNF over-expressing MSCs offer significant potential for the delivery of neurotrophic support to the Parkinsonian rat brain 24,25 , successful clinical translation will undoubtedly be hindered by the poor survival of MSCs following transplantation 16,24 . This concern is further corroborated by a recent study where autologous MSCs genetically engineered to over-express GDNF were unilaterally transplanted into the striatum and substantia nigra of cynomolgus monkeys 26 .…”

Section: Text Introductionmentioning

confidence: 97%

Fibrin As a Scaffold for Delivery of GDNF Overexpressing Stem Cells to the Adult Rat Brain

Moloney

Fhlathartaigh

Kulkarni

et al. 2015

ACS Biomater. Sci. Eng.

Self Cite

View full text Add to dashboard Cite

Treatment of neurodegenerative disease is entering a new era where direct intracerebral delivery of therapeutic factors aims to restore normality to dysfunctional circuits.Cell-based therapeutic approaches, where virally manipulated mesenchymal stem cells (MSCs) over-expressing glial cell line derived neurotrophic factor (GDNF) are utilised as vehicles to deliver neurotrophic support to the Parkinsonian brain, have shown promising pre-clinical results at preserving dopaminergic neuron integrity. However, poor cell survival following transplantation will hinder clinical progression. One approach to improve MSCs survival following transplantation is to couple the cell engraftment procedure with a scaffold thereby providing a physical substrate upon which to eventually complex pro-survival factors. Evaluation of commercially available, clinically accepted materials with an established safety profile will expedite clinical translation. Therefore, this study sought to determine if a clinically used fibrin scaffold can be utilised as an adjunct to intra-cerebral cell transplantation without evoking an adverse host or stem cell response. Sixteen male SpragueDawley rats received bilateral intra-striatal transplants of 30,000 GDNF-transduced MSCs delivered in either control transplantation medium or a fibrin scaffold. Rats were sacrificed 1, 4, 7, and 14 days post-transplantation. Brains were analysed to determine in situ polymerisation and biodegradability of the fibrin scaffold, GDNF release from transplanted GDNF-MSCs, survival of the GDNF-MSCs graft and the host's immune response to the transplant. This study found that fibrin scaffold was adaptable to intra-cerebral delivery with successful polymerisation of the fibrin scaffold in situ. Inclusion of the fibrin scaffold was not detrimental to cell survival nor did it impede neurotrophin release from entrapped cells.Importantly, the inclusion of the fibrin scaffold was associated with a reduced host astroglial and microglial response compared to cells alone indicative of a favourable biocompatibility profile. Overall, fibrin represents an adaptable scaffold for inclusion in a minimally invasive cell-based therapeutic approach for neurodegenerative diseases.TEXT Introduction:

show abstract

“…However, to the best of our knowledge, this has not been reported in patient postmortem analysis, perhaps in part because of the far larger brain volume. Hydrogels that form in situ (i.e., in the brain post injection) such as those formed from collagen used previously for delivery of stem cells to the brain [54], have the potential to form a means of retaining the grafted cells in a single transplant site. Alternatively, biomaterial spheres or scaffolds have been used to deliver GDNF to promote engraftment by improving graft integration in the brain [55,56].…”

Section: Could Cell Therapies Be Better Targeted?mentioning

confidence: 99%

Targeting delivery in Parkinson's disease

Newland

Dunnett

Dowd

2016

Drug Discovery Today

Self Cite

View full text Add to dashboard Cite

Disease-modifying therapies for Parkinson's disease (PD), with the potential to halt the neurodegenerative process and to stimulate the protection, repair, and regeneration of dopaminergic neurons, remain a vital but unmet clinical need. Targeting the delivery of current and new therapeutics directly to the diseased brain region (in particular the nigrostriatal pathway) could result in greater improvements in the motor functions that characterise PD. Here, we highlight some of the opportunities and challenges facing the development of the next generation of therapies for patients with PD.

show abstract

The reduction in immunogenicity of neurotrophin overexpressing stem cells after intra-striatal transplantation by encapsulation in an in situ gelling collagen hydrogel

Cited by 73 publications

References 50 publications

GDNF-secreting mesenchymal stem cells provide localized neuroprotection in an inflammation-driven rat model of Parkinson’s disease

GDNF-secreting mesenchymal stem cells provide localized neuroprotection in an inflammation-driven rat model of Parkinson’s disease

Fibrin As a Scaffold for Delivery of GDNF Overexpressing Stem Cells to the Adult Rat Brain

Targeting delivery in Parkinson's disease

Contact Info

Product

Resources

About