Plasmonic Photothermal and Stem Cell Therapy of Atherosclerosis Versus Stenting
Кључне речи
Апстрактан
Опис
Nanoparticles (NPs) are quite safe for an organism but entire kinetics is mostly unknown. The most dangerous approach with lowest level of efficacy and safety is a delivery of NPs with microbubbles. SP+ and mesenchymal SPCs have the similar efficacy as a local delivery system with a lot of beneficial properties such as anti-inflammative, anti-apoptotic, and multi-metabolic effects leading to the plaque degradation and artery rejuvenation. Thus, nanoburning is very challenging technique to demolish and reverse the plaque especially in combination with stem cell technologies promising functional restoration of the vessel wall and can be an alternative to stenting.
Altering general strategy the investigators generally offer:
1. The investigators don't need a therapy only with harvested stem cells (not so effective, but more provocative); the investigators have to manage host resident stem cells on site [local in-artery infusion] with growth factors, cytokines [or systemic potentiation, but risk of side effects and adverse events is high].
2. Regular intravenous systemic therapy with modified BM (bone marrow), circulating progenitor, and iPS (induced pluripotent) stem cells might be beneficial for prevention of diseases, and rejuvenation of tissues and organs - but the system as whole will be compromised [the investigators can store stem cells of each individual to use for cell therapy or bioengineering].
3. The best way - development of bioengineered constructions through life to transplant a bioartificial organ on request.
4. Multi-step invasive treatment of atherosclerosis - (1) biodegradable stenting in ACU (acute care unit), or preventively, with no restenosis and no acute atherothrombosis risk profile, (2) regular systemic or local stem cell therapy, or with cytokines, (3) on-artery MSCs (mesenchymal stem cells)-related bioengineered patch with silica-gold iron-bearing NPs [SCs (stem cells) as carriers for NPs with transduction in hands of magnetic fields for local elimination of plaque, and subsequent rejuvenation of artery wall.
Our new approach, challenging modern therapy of atherosclerosis include:
1. BIODEGRADABLE STENTS - for 6-24 months period under the soft short-term antithrombotic therapy (resolving concerns with stenosis/ lumen + steered remodeling); no hemorrhages, no alien metal body, no concerns with further CABG, minimal inflammation
2. INTRAVENOUS NON-SPECIFIC SYSTEMIC STEM CELL THERAPY - before and after stenting - launch repair effects in vessel + beneficial effects for ischemic or injured tissues
3. ON-ARTERY BIOENGINEERED PATCH transplantation with NPs or MICRO-INFUSION of stem cells bearing NP - grown with MSCs and NPs (bovine pericardium scaffold); 3-6 weeks to grow a thin structure (recover cells before or during stenting), multi-effects due to migration of SCs + bioactive products of lysis
4. PLASMONIC PHOTOTHERMAL THERAPY - 'melting' and 'burning' effects - direct degradation + bioactive products of stem cells' lysis + further migration of SCs from patch
Potential expected disadvantages of our approach: Necessity of the special precise delivery technique. Lost function of artery - irreparable pro-fibrotic and pro-inflammative damage - necessity of another clinical approach for restoration of tissue (may be with stem cells). Threat of acute fatal atherothrombosis due to rupture of (vulnerable) plaque - verification of the optimal antithrombotic therapy. Cannot treat non-organic part of plaque - necessity of the special therapy for mineral deposits, calcified necrotic core, fibrotic sites - solution using stem cells. Harm of potent detrimental adverse effects - vapor bubbling (boiling of cytoplasm and ECM with subsequent lysis of cells, and provocation of pro-apoptotic cascades), acoustic and shock waves due to plasma-generated laser-related detonation of nanoshells in tissue - need regenerative therapy (type of SCs, conditions and way of transplantation; Culturing? Sorting?). Erratic (unsteered) heating - surrounding tissue of the site of interest can achieve a temperature until 38-39°. But at the site of burning final temperature can be at about 50-180 C (cauterization/ searing/ melting effect) with consequent pro-fibrotic effect - need regenerative therapy and clarification of energy options.
Датуми
| Последња верификација: | 04/30/2015 |
| Фирст Субмиттед: | 09/13/2011 |
| Предвиђена пријава послата: | 09/15/2011 |
| Прво објављено: | 09/18/2011 |
| Послато последње ажурирање: | 05/16/2015 |
| Последње ажурирање објављено: | 05/18/2015 |
| Стварни датум почетка студије: | 11/30/2010 |
| Процењени датум примарног завршетка: | 06/30/2012 |
| Предвиђени датум завршетка студије: | 09/30/2012 |
Стање или болест
Интервенција / лечење
Other: Stenting + Micro-infusion
Device: Stenting
Фаза
Групе руку
| Арм | Интервенција / лечење |
|---|---|
| Experimental: Stenting + Micro-infusion Step 1 - implantation of everolimus-eluting stent with imaging by MSCT, IVUS and OCT; Step 2 - injection of stem cells containing gold nanoparticles with silica-iron oxide shells. | Other: Stenting + Micro-infusion Step 1 - IVUS, OCT-guided put in everolimus-eluting (drug-eluting-DES) stent + intravascular ultrasound (IVUS) mapping + harvesting stem cells with mesenchymal phenotype; Step 2 - culturing of stem cells in medium by gold nanoparticles with silica-iron oxide shells; Step 3 - micro-infusion of stem cells bearing NP into the lesion; Step 4 - detonation of nanoshells after migration of stem cells with NPs inside (until 7-10 days after transplantation). We expect 'melting' and 'burning' effects of PPTT, beneficial effects of bioactive products of stem cells lysis + benefits from further migration of stem cells from patch into the plaque |
| Active Comparator: Stenting Put in everolimus-eluting stent | Device: Stenting Put stent in ischemia-related coronary artery by indications for PCI |
Критеријуми
| Узраст подобан за студирање | 45 Years До 45 Years |
| Полови подобни за студирање | All |
| Прихвата здраве волонтере | да |
| Критеријуми | Inclusion Criteria: - Multivessel coronary artery disease without indications for CABG - Stable angina with indications for preventive PCI - NSTEMI (primary PCI and late comers) <=> 12 hr - STEMI with kept EF>50% (all comers) - Rescue PCI - Vessel size between 2.3-4.0 mm - NYHA II-III functional class of HF - De novo treatment = no history of PCI or CABG - Atherosclerosis of proximal left anterior descending artery <50% stenosis - Treated hypertension - Signed written informed consent Exclusion Criteria: - History of MI - History of CABG or PCI - Indications for CABG - Contraindications for CABG, PCI - History of unstable angina, coronary artery syndrome - History of arrhythmias - History of stroke - NYHA I, IV functional class of HF - Diabetes (fasting glucose > 7.0 mM/L) - Untreated hypertension - Asthma - Participation to any drug-investigations during previous 60 days - Pregnancy - Intolerance to any limus drugs, aspirin, clopidogrel, aspirin, metals and polymers of stent and nanoparticles - Need for chronic treatment with anti-vitamin K drugs - Impossibility of clinical follow-up |
Исход
Примарне мере исхода
1. Total atheroma volume [at month 12]
Секундарне мере исхода
1. Composite end-point of any MACE (major acute cardiovascular events), all-cause death, any revascularization [at month 12]
2. Composition of plaque [at month 12]
3. Major and minor bleeding [at month 12]
4. Restenosis rate [at month 12]
5. Stent thrombosis rate [at month 12]
6. Coronary flow-mediated vasodilatation [at month 12]
7. Coronary intima-media thickness [at month 12]
8. Minimum diameter stenosis [at month 12]
9. Minimum lumen diameter [at month 12]
