implantation-of-inferior-vena-cava-interposition-graft-in-mouse-model

Implantation of Inferior Vena Cava Interposition Graft in Mouse Model

Biodegradable scaffolds seeded with bone marrow mononuclear cells (BMCs) are often used for reconstructive surgery to treat congenital cardiac anomalies. ...

transplantation-pulmonary-valve-using-mouse-model-heterotopic-heart

Transplantation of Pulmonary Valve Using a Mouse Model of Heterotopic Heart Transplantation

Tissue engineered heart valves, especially decellularized valves, are starting to gain momentum in clinical use of reconstructive surgery with mixed ...

Nationwide Children's Hospital

Since most transplanted cells rapidly die in an ischemic environment by hypoxia and hyponutrition, it is crucial to know how to protect transplanted cells for improving transplantation efficiency. We examined whether the transduction of an artificial anti-cell death protein (PTD-FNK) into bone marrow mononuclear cells (BM-MNCs) prevents cell death and improves the transplantation efficiency of BM-MNCs in ischemic regions. Rat bone marrow cells were prepared from the femur and tibia and cultured on dishes precoated with human fibronectin in the absence of serum. BM-MNCs transduced with PTD-FNK survived better than those without the protein (P<0.008) and retained the potential to differentiate into endothelial progenitor cells (EPCs), as judged by the uptake of an acetylated low-density lipoprotein and the ability to bind lectin. Next, we used a co-culture system comprising human umbilical vein endothelial cells (HUVECs) and fibroblasts to examine angiogenic potential. HUVECs pretreated with PTD-FNK survived and formed a blood-vessel-like structure better than untreated cells (P<0.001). When BM-MNCs expressing EGFP were transplanted into ischemic areas of a male rat ischemic hindlimb model, the cells pretreated with PTD-FNK were incorporated into blood vessel with a higher efficiency than the untreated BM-MNCs (P=0.03). BM-MNCs protected through transduction of PTD-FNK maintained their angiogenic potential. Thus, PTD-FNK improves the transplantation efficiency of BM-MNCs into ischemic regions.

Transduction of the anti-apoptotic PTD-FNK protein improves the efficiency of transplantation of bone marrow mononuclear cells.

Churg-Strauss syndrome (CSS) causes necrotizing vasculitis affecting small- to medium-sized arteries, mainly in the lungs, gastrointestinal system, heart, kidneys, and skin. Skin lesions sometimes ulcerate because of severe ischemia and become intractable when complicated by bacterial infection. We report a rare case of CSS, characterized by a nonhealing ischemic skin ulcer of the right calf with bacterial infection resistant to antibiotics. After sterile maggot debridement therapy, 2 skin autografts failed. Subsequently, a slow-release formula of basic fibroblast growth factor incorporated in biodegradable gelatin hydrogel was administered into the calf muscles to induce vascular regeneration. The ulcer eventually healed with no recurrence. This report describes the use of controlled-release basic fibroblast growth factor for an ischemic leg ulcer in a patient with CSS, suggesting a possible therapeutic role of this novel neovascularization therapy in treating severe skin lesions complicating autoimmune vasculitis syndromes.

Therapeutic angiogenesis by controlled-release fibroblast growth factor in a patient with Churg-Strauss syndrome complicated by an intractable ischemic leg ulcer.

We examined the safety and efficacy of controlled-release basic fibroblast growth factor (b-FGF) for peripheral artery disease (PAD), compared with autologous bone marrow mononuclear cell implantation (BMCI).

Controlled-release basic fibroblast growth factor for peripheral artery disease: comparison with autologous bone marrow-derived stem cell transfer.

Novel approach to ischemic skin ulcer in systemic lupus erythematosus: therapeutic angiogenesis by controlled-release basic fibroblast growth factor.

Purpose: Despite advances in therapeutic angiogenesis by bone marrow cell implantation (BMCI), limb amputation remains a major unfavorable outcome in patients with critical limb ischemia (CLI). We sought to identify predictor(s) of limb salvage in CLI patients who received BMCI. Materials and Methods: Nineteen patients with CLI who treated by BMCI were divided into two groups; four patients with above-the-ankle amputation by 12 weeks after BMCI (amputation group) and the remaining 15 patients without (salvage group). We performed several blood-flow examinations before BMCI. Ankle-brachial index (ABI) was measured with the standard method. Transcutaneous oxygen tension (TcPO2) was measured at the dorsum of the foot, in the absence (baseline) and presence (maximum TcPO2) of oxygen inhalation. (99m)technetium-tetrofosmin ((99m)Tc-TF) perfusion index was determined at the foot and lower leg as the ratio of brain. Results: Maximum TcPO2 (p = 0.031) and (99m)Tc-TF perfusion index in the foot (p = 0.0068) was significantly higher in the salvage group than in the amputation group. Receiver operating characteristic (ROC) curve analysis identified maximum TcPO2 and (99m)Tc-TF perfusion index in the foot as having high predictive accuracy for limb salvage. Conclusion: Maximum TcPO2 and (99m)Tc-TF perfusion index in the foot are promising predictors of limb salvage after BMCI in CLI.

Prediction of limb salvage after therapeutic angiogenesis by autologous bone marrow cell implantation in patients with critical limb ischemia.

The development of vascular bioengineering has led to a variety of novel treatment strategies for patients with cardiovascular disease. Notably, combining biodegradable scaffolds with autologous cell seeding to create tissue-engineered vascular grafts (TEVG) allows for in situ formation of organized neovascular tissue and we have demonstrated the clinical viability of this technique in patients with congenital heart defects. The role of the scaffold is to provide a temporary 3-dimensional structure for cells, but applying TEVG strategy to the arterial system requires scaffolds that can also endure arterial pressure. Both biodegradable synthetic polymers and extracellular matrix-based natural materials can be used to generate arterial scaffolds that satisfy these requirements. Furthermore, the role of specific cell types in tissue remodeling is crucial and as a result many different cell sources, from matured somatic cells to stem cells, are now used in a variety of arterial TEVG techniques. However, despite great progress in the field over the past decade, clinical effectiveness of small-diameter arterial TEVG (<6mm) has remained elusive. To achieve successful translation of this complex multidisciplinary technology to the clinic, active participation of biologists, engineers, and clinicians is required.

Vessel bioengineering.

SSc causes intractable ischaemic ulcers. To avoid major amputation, we examined the safety and efficacy of therapeutic vascular angiogenesis for digital ulcers due to SSc.

Therapeutic vascular angiogenesis for intractable macroangiopathy-related digital ulcer in patients with systemic sclerosis: a pilot study.

Because direct application of low-energy shock waves induces angiogenesis, we investigated the safety and efficacy of this new therapy to develop a noninvasive method of repeatable therapeutic angiogenesis for treating peripheral arterial disease (PAD).

Low-energy extracorporeal shock wave therapy improves microcirculation blood flow of ischemic limbs in patients with peripheral arterial disease: pilot study.

Autologous grafts are used to repair atherosclerotic cardiovascular diseases; however, many patients lack suitable donor graft tissue. Recently, tissue engineering techniques have emerged to make biologically active blood vessels. We applied this technique to produce arterial grafts using established biodegradable materials without cell seeding. The grafts were evaluated in vivo for vessel remodeling during 12 months.

Evaluation of remodeling process in small-diameter cell-free tissue-engineered arterial graft.

We developed a prototype for a closed apparatus for assembling tissue engineered vascular grafts (TEVG) with the goal of creating a simple, operator-independent method for making TEVGs in order to optimize safety and enable widespread application of this technology. The TEVG is made by seeding autologous, bone marrow-derived mononuclear cells onto a biodegradable tubular scaffold and is the first man-made vascular graft to be successfully used in humans. A critical barrier, which has prevented the widespread clinical adoption of the TEVG, is that cell isolation, scaffold seeding, and incubation are performed using an open method. In order to reduce the risk of contamination, the TEVG is assembled in a clean room. Clean rooms are expensive to build, complex to operate, and are not available in most hospitals. In this investigation, we used an ovine model to compare the safety and efficacy of TEVGs created using either a standard density centrifugation-based open method or the new filter-based closed system. We demonstrated no graft-related complications and maintenance of growth capacity in TEVGs created using the closed apparatus. In addition, use of the closed system reduced the amount of time needed to assemble the TEVG by approximately 50%. Adaptation of similar methodologies may facilitate the safe translation and widespread use of other tissue engineering technologies.

ArticleTotal : 2	Year
Publication title Cited by 24	2014
Publication title Cited by 7	2014

Article	Year
Transduction of the anti-apoptotic PTD-FNK protein improves the efficiency of transplantation of bone marrow mononuclear cells. Journal of molecular and cellular cardiology\| PubMed ID: 17229437	2007
Therapeutic angiogenesis by controlled-release fibroblast growth factor in a patient with Churg-Strauss syndrome complicated by an intractable ischemic leg ulcer. The American journal of the medical sciences\| PubMed ID: 19701077	2009
Controlled-release basic fibroblast growth factor for peripheral artery disease: comparison with autologous bone marrow-derived stem cell transfer. Tissue engineering. Part A\| PubMed ID: 21810028	2011
Novel approach to ischemic skin ulcer in systemic lupus erythematosus: therapeutic angiogenesis by controlled-release basic fibroblast growth factor. Geriatrics & gerontology international\| PubMed ID: 21951777	2011
Prediction of limb salvage after therapeutic angiogenesis by autologous bone marrow cell implantation in patients with critical limb ischemia. Annals of vascular diseases\| PubMed ID: 23555423	2011
Vessel bioengineering. Circulation journal : official journal of the Japanese Circulation Society\| PubMed ID: 24334558	2013
Therapeutic vascular angiogenesis for intractable macroangiopathy-related digital ulcer in patients with systemic sclerosis: a pilot study. Rheumatology (Oxford, England)\| PubMed ID: 24390937	2014
Low-energy extracorporeal shock wave therapy improves microcirculation blood flow of ischemic limbs in patients with peripheral arterial disease: pilot study. Journal of Nippon Medical School = Nippon Ika Daigaku zasshi\| PubMed ID: 24614391	2014
Evaluation of remodeling process in small-diameter cell-free tissue-engineered arterial graft. Journal of vascular surgery\| PubMed ID: 24745941	2014
Comparison of a Closed System to a Standard Open Technique for Preparing Tissue Engineered Vascular Grafts. Tissue engineering. Part C, Methods\| PubMed ID: 24866863	2014

Shuhei Tara

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