Author Topic: (AAN) Decline in protective capacity of multipotent mesenchymal stromal cells ...  (Read 66 times)

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Offline agate

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Presented at the annual AAN conference in April 2016 (Vancouver, BC):

Quote
S2.007 - Neuroglial protective capacity of multipotent mesenchymal stromal cells declines with duration of progressive disease in multiple sclerosis
 
Dr Pamela Sarkar, Julianna Redondo, Kevin Kemp, Alastair Wilkins, N. Scolding, Claire M. Rice

Bristol, United Kingdom

Disclosures

 D. Sarkar: None. J. Redondo: None. K. Kemp: None. A. Wilkins: None. N. Scolding: None. C.M. Rice: None.

Objective/Background:


Over 80% of patients with multiple sclerosis (MS) develop progressive disease for which there is no disease modifying treatment. The potential of multipotent mesenchymal stromal cells (MSCs) for repair in MS has been extensively examined in vitro and clinical trials are now in progress.

We, and others, have demonstrated that MSCs have similar baseline characteristics irrespective of whether they are derived from the bone marrow of normal control subjects or patients with MS. However, the capacity of these cells for neuroglial protection in vitro has not been compared.

Methods:

MSCs were isolated from the bone marrow of participants in the ongoing clinical trial ‘Assessment of bone marrow-derived Cellular Therapy in progressive Multiple Sclerosis (ACTiMuS; NCT01815632)’.

We compared colony-forming and proliferative potential, differentiation potential and senescence of MSCs derived from patients with MS and from control subjects. Using in vitro models of neuroglial toxicity, we have also compared the protective properties of MSC-conditioned medium (MSCcm) derived from patients with MS and control subjects.

Results:

MSCs isolated from patients and controls are comparable in terms of proliferation and differentiation capacity but donor age negatively correlates with clonogenic potential and senescence. The neuroglial protective effects of MSCcm decline with expansion in vitro. MSCcm isolated from patients with MS affords reduced protection to neurons and glia; the effect cannot be accounted for by age of subjects but negatively correlates with duration of progressive disease.

Conclusion:

Our findings have important implications for those developing cellular therapy as a treatment for MS.

They suggest that the reparative capacity of MSCs to protect neurons and glia is affected by expansion ex vivo and with duration of MS disease progression.

Future work will employ proteomic techniques to explore the mechanisms underlying our observations.
« Last Edit: April 26, 2016, 03:29:19 pm by agate »
MS Speaks--online for 13 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010.

 

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