Page 84 - NNS 2014 Program & Abstract Book

and research management priorities as well as how the agencies will

begin to address them. Issues to be addressed regarding TBI include

development of a more precise classification system of TBI, identi-

fication of objective end points to improve the sensitivity of thera-

peutic trials, identification and organization of tissue repositories,

improving patient reintegration into society, enhancing sharing of

research data and investigation of means by which electronic medical

records can be utilized for epidemiologic and clinical studies. This

effort has stimulated closer coordination within and between the

federal neurotrauma and mental health fields which adds value to the

efforts given the frequencies of traumatic and psychological co-

morbidities. The National Neurotrauma Symposium offers an excel-

lent opportunity to share our progress and to seek feedback from the

research community.

1. Improving Access to Mental Health Services for Veterans, Service

Members, and Military Families. Executive Order. The White House.

2. National Research Action Plan.

Key words

federal funding agencies, research coordination, strategic planning

B2-01

MESOPOROUS SILICA NANOPARTICLES CAN DELIVER

PTEN INHIBITOR AND ENHANCE NEURONAL REGENERA-

TION EFFECTIVELY

Kim, M.S.

1

, Ahn, H.S.

1,3

, Hyun, J.K.

1–3

1

Department of Nanobiomedical Science & BK21PLUS Global Re-

search Center for Regenerative Medicine, Dankook University,

Cheonan, Korea

2

Department of Rehabilitation Medicine, College of Medicine, Dan-

kook University, Cheonan, Korea

3

Institute of Tissue Regeneration Engineering, Dankook University,

Cheonan, Korea

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN)

is known to regulate the axonal regrowth of central and peripheral

nervous systems, and PTEN inhibition can facilitate axonal out-

growth following nerve injury. However single application of PTEN

inhibitor to the injured neurons is not sufficient for long-term re-

generation of outgrowing axons. Mesoporous silica nanoparticle

(MSN) has a large surface area, high pore volume and intrinsic

biocompatibility which enable absorption and release of multiple

drugs and biomolecules. Therefore we planned to use MSN as a drug

delivery system for PTEN inhibitor, bisperoxovanadium (BpV)

(HOpic) through in vitro and in vivo studies for the first time. We

prepared dorsal root ganglion (DRG) from adult Sprague-Dawley

(SD) rats for in vitro study, and the cervical roots in SD rats were

crushed with forcep for 5 seconds for in vivo study. Various con-

centration of BpV, MSN and BpV-conjugated MSN was tested to

detect optimal condition for cell viability and axonal regeneration

for 5 days. We found that the application of 20ng BpV conjugated

with 20

l

g/ml MSN to primary cultured DRG showed the best cell

viability and maximal axonal outgrowth. With the same concentra-

tion, we injected BpV-conjugated MSN (1

l

g/per DRG) into the

damaged DRG in rats and found that outgrowing axons crossing

injury site were increased and faster than vehicle controls. We

conclude that mesoporous silica nanoparticles can deliver PTEN

inhibitor to neurons effectively and enhance neuronal regeneration

in vitro and in vivo conditions.

Key words

mesoporous nanoparticle, PTEN inhibition

B2-02

DIRECTLY REPROGRAMMED NEURAL STEM CELLS EN-

HANCE FUNCTIONAL RECOVERY FOLLOWING SPINAL

CORD INJURY IN RATS

Kim, J.

1,2

, Hong, J.Y.

1,2

, Han, D.W.

3,4

, Hyun, J.K.

1,2,5

1

Dankook University, Department of Nanobiomedical Science and

BK21PLUS Global Research Center for Regenerative Medicine,

Cheonan, South Korea

2

Dankook University, Institute of Tissue Regeneration Engineering,

Cheonan, South Korea

3

Dankook University, Department of Rehabilitation Medicine, Col-

lege of Medicine, Cheonan, South Korea

4

Konkuk University, Department of Stem Cell Biology, School of

Medicine, Seoul, South Korea

5

Konkuk University, Department of Animal Biotechnology, Seoul,

South Korea

Injured spinal cord is hard to be regenerated, and there is as yet no

proven fundamental treatment in the clinical setting. Regenerative

strategies using stem cells and biomaterials have revealed some

functional improvements following spinal cord injury (SCI) in the

experimental field, however there are many hurdles to be applied in

the clinical field. Direct reprogramming of somatic cells into neural

stem cells has many advantages including reduced tumorigenicity, no

need to perform additional in vitro differentiation before transplan-

tation, and multipotency only to differentiate into neural and glial

cells with capable of autologous transplantation. Recently, we re-

ported that mouse embryonic fibroblasts (MEFs) were directly con-

verted into the induced neural stem cells (iNSCs) using four

transcription factors (

Brn4

,

Sox2

,

Klf4

, and

c-Myc

) without the pro-

duction of induced pluripotent stem. We transplanted iNSCs into

contused spinal cord in Sprague-Dawley rats and found that locomotor

functions including Basso, Beattie, and Bresnahan (BBB) score and

ladder score were improved following iNSC transplantation more than

those in vehicle controls. Transplanted iNSCs were migrated and

differentiated well into neurons, astrocytes, and oligodendrocytes, and

formed synapse to host neurons within grafted site 12 weeks following

transplantation. The inflammatory cells including macrophages and

monocytes were reduced within the cavity in the injured site and the

cavity size was also reduced 12 weeks following transplantation. This

study is the first trial to investigate the effect and the therapeutic

potential of directly converted iNSCs from mouse fibroblasts in the rat

SCI model.

Key words

directly reprogrammed neural stem cell, in vivo differentiation, spinal

cord injury, transplantation

B2-03

USING TRANSCRIPTION FACTORS TO PROMOTE THE

SURVIVAL OF TRANSPLANTED CELLS FOR SPINAL CORD

INJURY REPAIR

Brown, J.L., Coothan Kandaswamy, V., Scorpio, K.A., Hill, C.E.,

Brown, J.L.

Burke-Cornell Medical Research Institute, White Plains, USA

Cellular transplants offer a multifaceted approach for spinal cord in-

jury (SCI) repair. Despite significant progress in understanding their

therapeutic potential, a common feature of all cell transplants, which

may have detrimental affects on the use of transplants clinically, is the

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