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

NCT02387749 | Completed Results DMC

• 1 other identifier: FACULTY OF MEDICINE,CAIRO U
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

Brief 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

Conditions

Diabetic Peripheral Neuropathy

Keywords

diabetic peripheral neuropathy; mesenchymal stem cells

Outcome Measures

Primary Outcomes (4)

• Measurement of b-FGF, v-EGF MEASURED BY ELISA

  measurement of b-FGF and v-EGF MEASURED BY ELISA before (at zero), and after at (7 days, 90) days after stem cell transfusion to measure the effect of stem cell and its role in nerve regeneration

  zero ( before) , 7 DAYS, 90 days

• Change of Nerve Conduction Velocities of Nerves Affected Measured by Nerve Conduction Study.

  Measuring nerve conduction velocities(NCV) in m/sec upper and lower limbs nerves(sensory and motor) lower limb nerves : tibial , common peroneal(CP) as motor and sural nerve as sensory upper limb nerves: ulnar nerve as motor and sensory and compare at base line(zero day) and 90 days after stem cells transfusion

  base line(zero dya), 90 days after stem cells transfusion.

• Change of Nerve Conduction Latency of Nerves Affected Measured by Nerve Conduction Study

  Measuring nerve conduction latency in msec of upper and lower limbs nerves(sensory and motor) lower limb nerves : tibial , common peroneal(CP) as motor and sural nerve as sensory upper limb nerves: ulnar nerve as motor and sensory and compare at base line and 90 days after stem cells transfusion

  base line(zero dya), 90 days after stem cells transfusion .

• Change of Nerve Conduction Amplitude of Nerves Affected Measured by Nerve Conduction Study.

  Measuring nerve conduction amplitudes in uv of upper and lower limbs nerves(sensory and motor). lower limb nerves : tibial , common peroneal(CP) as motor and sural nerve as sensory . upper limb nerves: ulnar nerve as motor and sensory. and compare at base line and 90 days after stem cells transfusion

  base line(zero dya), 90 days after stem cells transfusion

Secondary Outcomes (2)

• Change of Levels of Fasting Blood Sugar and 2 Hours Post Prandial at Base Line ( Zero Day ) and After (90 Days) After Stem Cells Transfusion

  base line (zero day) and 90 days after stem cells transfusion

• Change of Levels of Glycated Haemoglobin( HA1C) After Stem Cells Transfusion Measured in Percent %

  at base line (zero day) and 90 days after stem cells transfusion

Study Arms (1)

mesenchymal stem cells

EXPERIMENTAL

The BM aspirate will be diluted at 6:1 ratio with phosphate buffer saline with 2 ml EDTA (30 ml BM aspirate+ 5 ml PBS/EDTA buffer).MNCs will be separated under aseptic conditions using a Ficoll. Hypaque desity gradient by centrifugation at 1800 rpm for 20 min then the MNCs will be plated in 40 ml(αMEM), serum free media; mesencult(MSCs culture),penicillin (100 U/ml),streptomycin(10 mg/ml),0.5 ml amphotericin B(all from Gibco BRL) and 10 ng/ml basic fibroblast growth factor (b-FGF)(R\&D system, Minneapolis, MN) and will be incubated at 370 c in a humidified atmosphere containing 5% CO2 .after one day ,nonadherent cells will be cultured in the presence of Mesenchymal media for 3 weeks changed every week. After reaching 80% confluence the MSCs will be placed in 10 ml saline and infused IV.

Genetic: mesenchymal stem cells

Interventions

mesenchymal stem cells GENETIC

collection of stem cells by bone marrow biopsy from iliac crest, then culture for 1 month , then IV transfusion on 2 sessions to the same patient

mesenchymal stem cells

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• (Type I, type II) diabetic patients age range (18-45) years, with diabetic peripheral neuropathy proved by clinical assessment and nerve conduction who did not receive treatment for diabetic peripheral neuropathy.

You may not qualify if:

• Decompensated cardiac, renal or liver disease. Associated autoimmune diseases Associated endocrinal diseases Pregnancy, usage of contraceptive pills or steroids.

Sponsors & Collaborators

• Cairo University: lead

Related Publications (11)

• 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.

  PMID: 17495381 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.

  PMID: 16779672 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.

  PMID: 15321945 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.

  PMID: 14706061 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.

  PMID: 16644707 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.

  PMID: 16326870 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.

  PMID: 18728233 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.

  PMID: 10938049 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.

  PMID: 10583212 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.

  PMID: 18220646 BACKGROUND

• 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.

  PMID: 39435603 DERIVED

Limitations and Caveats

patients are not so co-operative regarding stem cell collection by bone marrow biopsy, Lab requirements for stem cell culture and follow up are limited to the university lab with expensive equipment and kits The sample is small

Results Point of Contact

• Title: Dina Mohammed Riad Ebrahim Abdelmagid
• Organization: Cairo university, faculty of medicine

drdina_m@hotmail.com

+201112052600

Study Officials

• Mohamed Gamal ElDin Saadi, phd

  Cairo University

  STUDY CHAIR

• Dina Abdelmagid, MD, MRCP UK

  Cairo University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Lecturer of Internal Medicine,faculty of medicine,Kasr Al Ainy hospital

Study Record Dates

• First Submitted: March 1, 2015
• First Posted: March 13, 2015
• Study Start: May 1, 2014
• Primary Completion: August 1, 2016
• Study Completion: December 1, 2016
• Last Updated: July 3, 2018
• Results First Posted: October 11, 2017

Record last verified: 2018-07