Effect Of Mesenchymal Stem Cells Transfusion on the Diabetic Peripheral Neuropathy Patients .

Summary

A debilitating consequence of diabetes mellitus (DM) is neuropathy which globally affects between 20 -30% of diabetic patients and up to 50% in other studies. The incidence of diabetic neuropathy (DN) is estimated to be up to 45% for type 2 diabetic patients and 59% for type 1diabetic patients in USA.(DN) is the most common complication of DM.The pathophysiology of DN is promoted by several risk factors: micro vascular disease, neural hypoxia, and hyperglycemia-induced effects.At the molecular level, the primary cause of diabetic complications is known to be hyperglycemia, which disrupts cellular metabolism by the formation of reactive oxygen species (ROS).In the aspect of nerve functions, ROS formation increases neuron's susceptibility to damage. In addition, hyperglycemia impedes production of angiogenic and neurotrophic growth factors, which are necessary for normal function of neurons and glial cells and maintenance of vascular structure.No definitive disease-modifying treatments have been to reverse DN. The current treatment focuses on tight glycemic control which can reduce potential risk factors for further nerve damage and DN-associated pain management.In many studies, deficiency of neurotrophic factors and lack of vascular support have been regarded as key factors in the development DN.Mesenchymal stem cells (MSCs) are particularly attractive therapeutic agents because of their ability to self-renew, differentiate into multi lineage cell types, and locally secrete angiogenic cytokines, including basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) .These factors were reported to prompt neovascularization and have support for neural regeneration.It was plausible that MSCs may also be an effective therapeutic agent for the DN treatment through the paracrine effects of bFGF (Shibata et al., 2008) and VEGF and their potential to differentiate into neural cells such as astrocytes, oligodendrocytes , and Schwann cells.The adherent nature of MSCs makes them easy to expand in culture and an attractive candidate to use in cell therapy.Therefore, cell therapy has recently emerged as an attractive therapeutic strategy to meet the needs of both neurotrophic and vascular deficiencies of DN.Proper diagnosis of DN depends on the pattern of sensory loss, reflex test, electrodiagnostic studies, and imaging

Timeline

Start

2014-05

Primary completion

2016-08

Completion

2016-12

Publications

• Background Jackson L, Jones DR, Scotting P, Sottile V. Adult mesenchymal stem cells: differentiation potential and therapeutic applications. J Postgrad Med. 2007 Apr-Jun;53(2):121-7. doi: 10.4103/0022-3859.32215.
• Background Keilhoff G, Stang F, Goihl A, Wolf G, Fansa H. Transdifferentiated mesenchymal stem cells as alternative therapy in supporting nerve regeneration and myelination. Cell Mol Neurobiol. 2006 Oct-Nov;26(7-8):1235-52. doi: 10.1007/s10571-006-9029-9. Epub 2006 Jun 16.
• Background Kinnaird T, Stabile E, Burnett MS, Epstein SE. Bone-marrow-derived cells for enhancing collateral development: mechanisms, animal data, and initial clinical experiences. Circ Res. 2004 Aug 20;95(4):354-63. doi: 10.1161/01.RES.0000137878.26174.66.
• Background Morbach S, Lutale JK, Viswanathan V, Mollenberg J, Ochs HR, Rajashekar S, Ramachandran A, Abbas ZG. Regional differences in risk factors and clinical presentation of diabetic foot lesions. Diabet Med. 2004 Jan;21(1):91-5. doi: 10.1046/j.1464-5491.2003.01069.x.
• Background Nakae M, Kamiya H, Naruse K, Horio N, Ito Y, Mizubayashi R, Hamada Y, Nakashima E, Akiyama N, Kobayashi Y, Watarai A, Kimura N, Horiguchi M, Tabata Y, Oiso Y, Nakamura J. Effects of basic fibroblast growth factor on experimental diabetic neuropathy in rats. Diabetes. 2006 May;55(5):1470-7. doi: 10.2337/db05-1160.
• Background Rathur HM, Boulton AJ. Recent advances in the diagnosis and management of diabetic neuropathy. J Bone Joint Surg Br. 2005 Dec;87(12):1605-10. doi: 10.1302/0301-620X.87B12.16710. No abstract available.
• Background Shibata T, Naruse K, Kamiya H, Kozakae M, Kondo M, Yasuda Y, Nakamura N, Ota K, Tosaki T, Matsuki T, Nakashima E, Hamada Y, Oiso Y, Nakamura J. Transplantation of bone marrow-derived mesenchymal stem cells improves diabetic polyneuropathy in rats. Diabetes. 2008 Nov;57(11):3099-107. doi: 10.2337/db08-0031. Epub 2008 Aug 26.
• Background Adler AI, Stratton IM, Neil HA, Yudkin JS, Matthews DR, Cull CA, Wright AD, Turner RC, Holman RR. Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study. BMJ. 2000 Aug 12;321(7258):412-9. doi: 10.1136/bmj.321.7258.412.
• Background Digirolamo CM, Stokes D, Colter D, Phinney DG, Class R, Prockop DJ. Propagation and senescence of human marrow stromal cells in culture: a simple colony-forming assay identifies samples with the greatest potential to propagate and differentiate. Br J Haematol. 1999 Nov;107(2):275-81. doi: 10.1046/j.1365-2141.1999.01715.x.
• Background Dalla Paola L, Faglia E. Treatment of diabetic foot ulcer: an overview strategies for clinical approach. Curr Diabetes Rev. 2006 Nov;2(4):431-47. doi: 10.2174/1573399810602040431.
• Aldali F, Deng C, Nie M, Chen H. Advances in therapies using mesenchymal stem cells and their exosomes for treatment of peripheral nerve injury: state of the art and future perspectives. Neural Regen Res. 2025 Nov 1;20(11):3151-3171. doi: 10.4103/NRR.NRR-D-24-00235. Epub 2024 Oct 22.

Drugs

Indications