Arash Sarveazad1, Asrin Babahajian2, Mehrdad Bakhtiari3, Mansoureh Soleimani4, Babak Behnam5, Abazar Yari6, Abolfazl Akbari7, Mahmoud Yousefifard8, Atousa Janzadeh8, Naser Amini9, Shahram Agah7, Ali Fallah10, Mohammad Taghi Joghataei11. 1. Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran; Cellular and Molecular Research Center, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. 2. Liver & Digestive Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran. 3. Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. 4. Cellular and Molecular Research Center, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran; Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. 5. Department of Medical Genetics and Molecular Biology, Iran University of Medical Sciences (IUMS), Tehran, Iran; NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, Bethesda, Maryland, USA Office of the Clinical Director, NHGRI, National Institutes of Health, Bethesda, MD, USA. 6. Department of Anatomy, Faculty of Medicine, Alborz University of Medical Sciences, Karaj, Iran. 7. Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran. 8. Physiology Research Center and Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. 9. Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. 10. Mede Bioeconomy Company, Tehran, Iran. 11. Cellular and Molecular Research Center, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran; Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address: Mt.joghataei@yahoo.com.
Abstract
BACKGROUND: Although stem cell therapy has become a major focus as a new option for management of spinal cord injury (SCI), its effectiveness should be promoted. In this study, we investigated the effects of co-administrating human adipose-derived stem cells (hADSCs) and Chondroitinase ABC (ChABC) in a rat model of spinal cord injury. MATERIAL AND METHODS: hADSCs derived from superficial layer of abdominal adipose tissue were used to treat a contusion-induced SCI. Animals were randomly allocated to five equal groups including sham (only laminectomy), SCI (SCI+vehicle injection), hADSCs (1×10⁶ hADSCs/10μl intra-spinal injection), ChABC (10μl of 100U/ml ChABC intra-spinal injection injection), and hADSCs+ChABC. Basso, Beattie and Bresnahan tests were used to evaluate locomotor function. 8weeks after treatment, cavity size, myelination, cell differentiation (neuron and astrocyte), and chondroitin sulfate amount were analyzed. RESULTS: hADSC transplanted animals, ChABC injected animals (P<0.001), and hADSC+ChABC treated rats (P<0.001) displayed significant motor improvement compared to SCI group. Combination therapy of hADSCs and ChABC led to greater locomotor recovery compared to using hADSCs (P<0.001) or ChABC (P<0.01) alone. Spinal cords in the combined and single therapy groups had cavities filled with myelinated areas and less chondroitin sulfate content in comparison with the control group (P<0.001). hADSCs expressed GFAP, B III tubulin and Map2. CONCLUSION: Combination therapy with ChABC and hADSCs exhibits more significant functional recovery than single therapy using either. This result may be applicable in selection of the best therapeutic strategy for SCI.
BACKGROUND: Although stem cell therapy has become a major focus as a new option for management of spinal cord injury (SCI), its effectiveness should be promoted. In this study, we investigated the effects of co-administrating human adipose-derived stem cells (hADSCs) and Chondroitinase ABC (ChABC) in a rat model of spinal cord injury. MATERIAL AND METHODS: hADSCs derived from superficial layer of abdominal adipose tissue were used to treat a contusion-induced SCI. Animals were randomly allocated to five equal groups including sham (only laminectomy), SCI (SCI+vehicle injection), hADSCs (1×10⁶ hADSCs/10μl intra-spinal injection), ChABC (10μl of 100U/ml ChABC intra-spinal injection injection), and hADSCs+ChABC. Basso, Beattie and Bresnahan tests were used to evaluate locomotor function. 8weeks after treatment, cavity size, myelination, cell differentiation (neuron and astrocyte), and chondroitin sulfate amount were analyzed. RESULTS: hADSC transplanted animals, ChABC injected animals (P<0.001), and hADSC+ChABC treated rats (P<0.001) displayed significant motor improvement compared to SCI group. Combination therapy of hADSCs and ChABC led to greater locomotor recovery compared to using hADSCs (P<0.001) or ChABC (P<0.01) alone. Spinal cords in the combined and single therapy groups had cavities filled with myelinated areas and less chondroitin sulfate content in comparison with the control group (P<0.001). hADSCs expressed GFAP, B III tubulin and Map2. CONCLUSION: Combination therapy with ChABC and hADSCs exhibits more significant functional recovery than single therapy using either. This result may be applicable in selection of the best therapeutic strategy for SCI.