Side Effects of 4 Times Bone Marrow Mono Nuclear Transplantation in Patients With Ischemic Lower Limb

Study Overview
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Brief Summary
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Critical limb ischemia (CLI) results from severe occlusive disease that impairs distal limb perfusion to the point where oxygen delivery is no longer adequate to meet the metabolic needs of the tissue, even under resting conditions. The limits of peripheral artery disease (PAD) compensatory mechanisms, such as distal vasodilatation and collateral formation, have been exceeded at this point. PAD is a widespread disease, affecting up to 15% of all adults older than 55 years. Formation of true new blood vessels, or angiogenesis, and development of collateral vessels from preexisting blood vessels, or arteriogenesis, is important in the pathophysiology of vascular disease. By stimulating these processes the investigators might be able to provide an alternative treatment strategy for patients with lower limb ischemia. In response to tissue injury and remodeling, neovascularization usually occurs via the proliferation and migration of progenitor endothelial cells (EPC) from preexisting vasculature. Indeed, recent studies have shown that bone-marrow mononuclear cell (BM-MNC) implantation increases collateral vessel formation in patients with limb ischemia. So the investigators determine to evaluate the efficacy of repeated MNC transplantation in patients with ischemic lower limb.

Detailed Description
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In this study we transparent bone marrow derived mononuclear stem cells 4 times to the ischemic limb of 11 patients with PAD.first of all all the patients evaluate by physical examination,PFWD,ABI and serologic tests.then underwent bone marrow aspiration to take sample.In our lab the MNC are separated and divided in to equal doses.one of them inject to the ischemic foot and the othr one are freezed and inject after 3weeks.3 weeks after second injection again patient underwent bone marrow aspiration and the same process repeat.then after 4times transplantation,patients are followed up after 1,3,6,9,12 months after injection and evaluate by physical examination,PFWD,ABI and serologic tests.all the data are collected and analysed and the result will be shown.3 patients underwent cell transplantation just one time due to one time bone marrow aspiration.They are followed up after 1,3,6,9,12 months after injection and evaluate by physical examination,PFWD,ABI and serologic tests.at the end of the study patients with 4imes injection and 1time injection will be compared.

Official Title
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Evaluation the Side Effects of Repeated Bone Marrow Derived Mono Nuclear Stem Cells Transplantation in Patients With Lower Limb Ischemic Ulcer

Conditions
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Ischemic Ulcer

Intervention / Treatment
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* Biological: 4times injection
* Biological: stem cell transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ischemic lower limb based on TASK guide line Rutherford score:2,3 ABI<0.6 Absolute ankle pressure < 60 mmHg Both gender Age:20-62years Exclusion Criteria: EF<30% Cr>2 HbA1c>8% Bone marrow disorders:leukemia Cognitive disorders Infections MI with ST elevation during last month Malignancy Immunologic or rheumatologic disorders

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 62 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 4times injection<br>the patients with ischemic lower limb ulcer who underwent 4times stem cell injection. | Biological: 4times injection<br>* bone marrow derived mono nuclear stem cell<br>|
| Experimental: one injection<br>Patients with peripheral artery disease underwent cell transplantation just one time. | Biological: stem cell transplantation<br>* Mono nuclear stem cell transplantation by intra muscular injection to the ischemic lower limb<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| side effects | evaluation the side effect of cell injection like:allergic reaction,fever,skin eruption,pain increasing,decrease in walking distance,ulcer severity | 3months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFWD | Evaluation the pain free walking distance after cell transplantation. | 3months | 
| ABI | evaluation the improvement the score of ABI after stem cell transplantation . | 3months | 
| size and depth of ulcer | evaluation the improvement of ulcer by measuring the size and depth of ulcer in millimeter after transplantation. | 3months | 
| Amputation | Evaluation the need of limb amputation because of worsening the ulcer after cell injection. | 6months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bone marrow mono nuclear stem cell ischemic ulcer