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Kkot Nim Kang,
Da Yeon Kim,
So Mi Yoon,
Ju Young Lee,
Bit Na Lee,
Jin Seon Kwon,
Hyo Won Seo,
Il Woo Lee,
Ha Cheol Shin,
Young Man Kim,
Hyun Soo Kim,
Jae Ho Kim,
Byoung Hyun Min,
Hai Bang Lee,
Moon Suk Kim
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ABSTRACT: The present study employed a combinatorial strategy using poly(D,L-lactide-co-glycolide) (PLGA) scaffolds seeded with human mesenchymal stem cells (hMSCs) to promote cell survival, differentiation, and neurological function in a completely transected spinal cord injury (SCI) model. The SCI model was prepared by complete removal of a 2-mm length of spinal cord in the eighth-to-ninth spinal vertebra, a procedure that resulted in bilateral hindlimb paralysis. PLGA scaffolds 2 mm in length without hMSCs (control) or with different numbers of hMSCs (1 × 10(5), 2 × 10(4), and 4 × 10(3)) were fitted into the completely transected spinal cord. Rats implanted with hMSCs received Basso-Beattie-Bresnahan scores for hindlimb locomotion of about 5, compared with ~2 for animals in the control group. The amplitude of motor-evoked potentials (MEPs) averaged 200-300 μV in all hMSC-implanted SCR model rats. In contrast, the amplitude of MEPs in control group animals averaged 135 μV at 4 weeks and then declined to 100 μV at 8 weeks. These results demonstrate functional recovery in a completely transected SCI model under conditions that exclude self-recovery. hMSCs were detected at the implanted site 4 and 8 weeks after transplantation, indicating in vivo survival of implanted hMSCs. Immunohistochemical staining revealed differentiation of implanted hMSCs into nerve cells, and immunostained images showed clear evidence for axonal regeneration only in hMSC-seeded PLGA scaffolds. Collectively, our results indicate that hMSC-seeded PLGA scaffolds induced nerve regeneration in a completely transected SCI model, a finding that should have significant implications for the feasibility of therapeutic and clinical hMSC-delivery using three-dimensional scaffolds, especially in the context of complete spinal cord transection.
Biomaterials 04/2012; 33(19):4828-35. · 7.40 Impact Factor
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Kkot Nim Kang,
Da Yeon Kim,
So Mi Yoon,
Jin Seon Kwon,
Hyo Won Seo,
E Sle Kim,
Bong Lee,
Jae Ho Kim,
Byoung Hyun Min,
Hai Bang Lee,
Moon Suk Kim
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ABSTRACT: We aimed to develop a delivery system capable of maintaining a sustained release of protein drugs at specific sites using potentially biocompatible biomaterials. Here, we used bovine serum albumin (BSA) as a test protein to explore the potential utility of an injectable small intestine submucosa (SIS) as a depot for protein drugs. The prepared SIS powder was dispersed in PBS. The SIS suspension easily entrapped BSA in pharmaceutical formulations at room temperature. When this was suspension subcutaneously injected into rats, it gelled, forming an interconnecting three-dimensional network SIS structure to allow BSA to penetrate through it. The amount of BSA-FITC released from the SIS gel was determined in rat plasma and monitored by real-time in vivo molecular imaging. The data indicated the sustained release of BSA-FITC for 30 days in vivo. In addition, SIS gel provoked little inflammatory response. Collectively, our results show that the SIS gel described here could serve as a minimally invasive therapeutics depot with numerous benefits compared to other injectable biomaterials.
International journal of pharmaceutics 09/2011; 420(2):266-73. · 2.96 Impact Factor
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Kkot Nim Kang,
Ju Young Lee,
Da Yeon Kim,
Bit Na Lee,
Hyun Hee Ahn,
Bong Lee,
Gilson Khang,
So Ra Park,
Byoung Hyun Min,
Jae Ho Kim,
Hai Bang Lee,
Moon Suk Kim
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ABSTRACT: Using a complete spinal cord transection model, the present study employed a combinatorial strategy comprising rat bone marrow stem cells (rBMSCs) and polymer scaffolds to regenerate neurological function after spinal cord injury (SCI) of different lengths. SCI models with completely transected lesions were prepared by surgical removal of 1 mm (SC1) or 3 mm (SC3) lengths of spinal cord in the eighth-to-ninth spinal vertebrae, a procedure that resulted in bilateral hindlimb paralysis. A cylindrical poly(D,L-lactide-co-glycolide)/small intestinal submucosa scaffold 1 or 3 mm in length with or without rBMSCs was fitted into the completely transected lesion. Rats in SC1 and SC3 groups implanted with rBMSC-containing scaffolds received Basso-Beattie-Bresnahan scores for hindlimb locomotion of 15 and 8, respectively, compared with ∼3 for control rats in SC1-C and SC3-C groups implanted with scaffolds lacking rBMSCs. The amplitude of motor-evoked potentials recorded in the hindlimb area of the sensorimotor cortex after stimulation of the injured spinal cord averaged ∼100 μV in SC1-C and 10-50 μV in SC3-C groups at 4 weeks, and then declined to nearly zero at 8 weeks. In contrast, the amplitude of motor-evoked potentials increased from ∼300 to 350 μV between 4 and 8 weeks in SC1 rats and from ∼200 to ∼250 μV in SC3 rats. These results demonstrate functional recovery in rBMSC-transplanted rats, especially those with smaller defects. Immunohistochemically stained sections of the injury site showed clear evidence for axonal regeneration only in rBMSC-transplanted SC1 and SC3 models. In addition, rBMSCs were detected at the implanted site 4 and 8 weeks after transplantation, indicating cell survival in SCI. Collectively, our results indicate that therapeutic rBMSCs in a poly(D,L-lactide-co-glycolide)/small intestinal submucosa scaffold induced nerve regeneration in a complete spinal cord transection model and showed that functional recovery further depended on defect length.
Tissue Engineering Part A 06/2011; 17(17-18):2143-52. · 4.64 Impact Factor
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ABSTRACT: Several recent studies have demonstrated that stem cell differentiation can be generated by derivatives of retinoic acid. In this study we chose retinoic acid (RA) for inducing neural differentiation of rat muscle-derived stem cells (rMDSCs). rMDSCs were pre-induced with 10 ng/ml basic fibroblast growth factor (bFGF) and then treated with 2 μM RA. After stimulation, RA induced rMDSCs to have a neural-like morphology after 1-7 days of in vitro differentiation. In the results of immunocytochemistry, rMDSC treated with RA showed abundant positive cells against the neuronal markers neuronal-specific enolase (NSE) and tubulin-βIII (Tuj1). Also, 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase)-positive cells were observed, indicating oligodendrocyte lineage cells. However, positive cells against glial fibrillary acidic protein (GFAP), marker of astrocytes, were not detected. The mRNA profile of these cells included higher expression of NSE compared with those of non-treated cells in real-time PCR. From the data in this work, we suggest that rMDSCs can trans-differentiate into a neural-like phenotype under the RA conditions.
Journal of Tissue Engineering and Regenerative Medicine 05/2011; 5(5):410-4. · 3.28 Impact Factor
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ABSTRACT: The main goal of this work was to develop an optimal self-microemulsifying paclitaxel prepared with PLGA and solubilizer such as tetraglycol, Cremophor ELP, and Labrasol. The prepared PTx-loaded SMES showed the size of the range of 80-130 nm by dynamic light scattering and a spherical shape by atomic force mi-croscopy. In experiment of storage stability in deion-ized water (DW) or blood condition, PTx-loaded SMES showed good stability in DW and comparable stability in blood condition at 37˚C for 7 days. In ad-dition, PTx-loaded SMES showed a significant in-hibitory effect on B16F10 melanoma proliferation. In conclusion, we confirmed that the formulations tried in this study could be used as administration form for animal trials of PTx.
Journal of biomedical science and engineering 01/2011; 445044:352-356.
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ABSTRACT: The aim of this paper was to prepare a self-microemulsifying docetaxel (Dtx) using PLGA, Tetraglycol, Labrasol, and Cremophor ELP. The prepared Dtx-loaded self-microemulsifying system (SMES) showed the initial size of the range of 80–100 nm with narrow size distribution and the negative zeta-potential values. Its morphology was a spherical shape by atomic force microscopy. In experiment of stability, Dtx-loaded SMES prepared in DW and BSA condition showed good stability at 37 • C for 7 days. The viability of the B16F10 cells incubated with Dtx-loaded SMES, Dtx-solution, and Taxol were decreased as a function of incubation time. In conclusion, we confirmed that Dtx-loaded SMES showed an inhibitory effect for proliferation of B16F10 melanoma cells.
Hindawi Publishing Corporation Journal of Nanomaterials Article ID. 01/2011; 860376(6).
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ABSTRACT: The aim of this paper was to prepare a self-microemulsifying docetaxel (Dtx) using PLGA, Tetraglycol, Labrasol, and Cremophor ELP. The prepared Dtx-loaded self-microemulsifying system (SMES) showed the initial size of the range of 80-100nm with narrow size distribution and the negative zeta-potential values. Its morphology was a spherical shape by atomic force microscopy. In experiment of stability, Dtx-loaded SMES prepared in DW and BSA condition showed good stability at 37°C for 7 days. The viability of the B16F10 cells incubated with Dtx-loaded SMES, Dtx-solution, and Taxol were decreased as a function of incubation time. In conclusion, we confirmed that Dtx-loaded SMES showed an inhibitory effect for proliferation of B16F10 melanoma cells.
Journal of Nanomaterials 01/2011; 2011:7. · 1.38 Impact Factor
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Yun Mi Kang,
Bit Na Lee,
Jae Hoon Ko,
Gyeong Hae Kim, Kkot Nim Kang,
Da Yeon Kim,
Jae Ho Kim,
Young Hwan Park,
Heung Jae Chun,
Chun Ho Kim,
Moon Suk Kim
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ABSTRACT: In this work, we examined the biocompatibility of electrospun chitosan microfibers as a scaffold. The chitosan microfibers showed a three-dimensional pore structure by SEM. The chitosan microfibers supported attachment and viability of rat muscle-derived stem cells (rMDSCs). Subcutaneous implantation of the chitosan microfibers demonstrated that implantation of rMDSCs containing chitosan microfibers induced lower host tissue responses with decreased macrophage accumulation than did the chitosan microfibers alone, probably due to the immunosuppression of the transplanted rMDSCs. Our results collectively show that chitosan microfibers could serve as a biocompatible in vivo scaffold for rMDSCs in rats.
International Journal of Molecular Sciences 01/2010; 11(10):4140-8. · 2.60 Impact Factor
