In recent years, the so-called minimally manipulated cell products are increasingly popular worldwide. These are products that can be obtained within one surgical procedure (biomaterial sampling – processing – product injection) without the laboratory culturing stage. The adipose tissue stromal vascular fraction (SVF) is one of these products. On the global market there are some special medical devices for obtaining SVF directly in the operating room, “at the surgical table” in a closed system that requires minimal participation of the operator. So far, only two of these devices have been granted Marketing Authorization in the Russian Federation. Providing a number of advantages to a medical practitioner (no need in a specialized laboratory, no culturing phase, the probability of human error is minimized, autologous use, short processing phase, proven safety etc.), SVF has been widely used in healthcare, specifically in trauma care, urology, gynecology, cardiology, endocrinology, neurology etc. Reconstructive surgeries with SVF usage are included into the state healthcare services reimbursement programs in a number of countries (Japan, France).
Along with its wide clinical application, there is still a range of important questions, answers to which can significantly expand the area of SVF application.
Thus, different subjects can have various therapeutic effect. And this is due to the fact that the number of SVF cells per unit of the adipose tissue volume, the subpopulation cell composition and immunophenotype are variable and may depend on the donor’s age, gender, lifestyle and anatomical localization of the adipose tissue used to obtain the cell product.
Stromal vascular fraction of adipose tissue is a complex of cell populations with regenerative characteristics. An important component of SVF are stromal cells of adipose tissue, that are capable of self-renewal and multipotent differentiation. Their plasticity makes them prospective objects of cell therapy, which can be used in the treatment of various diseases.
At the process of preparation, cells are not subject to cultivation or other aggressive impacts. The process presents treating adipose tissue with an enzyme in quite low concentration in order to destroy collagen fibers, structural elements of adipose tissue. It leads to the release of blood vessel cells (endothelial, smooth muscle cells, and pericytes), blood cells (white blood cells, macrophages) and those of the connective tissue frame (fibroblasts). The ratio of these cell populations is unique for every person and remains unchanged in the process of therapeutic product harvesting. Cells are neither stimulated nor built up, which helps to avoid the risks associated with unwanted activation due to the influence of proteins of animal origin used in cultivation.
The adipose tissue is loose connective tissue. The adipose tissue mainly consists of adipocytes, organized into groups called lobules. Stroma, loose connective tissue, is located between lobules. Adipose tissue stroma separates lobules from one another like supportive septa. It has vessels and nerves. Stroma is also located inside lobules where it supports individual adipocytes. Lobular stroma has collagen fibers, a lot of capillaries that twine round adipocytes forming a net, and various cell types, such as mast cells, macrophages, and fibroblasts.
Normally, the adipose tissue accounts for 15-20% of the body mass in men and 20-25% – in women. Anorexia is associated with significant reduction in the adipose tissue content (up to 3%), and obesity – with its significant increase. The adipose tissue is present throughout the human body, not just in the form of subcutaneous deposits, but also around internal organs, forming sort of “pillows” around them.
The adipose tissue is metabolically active. Its main function is extracting fats (lipids) from blood, their synthesis, storage and mobilization. The fat is stored in adipocytes at the body temperature in a liquid state in the form of oil. Such fat consists of triglycerides – molecules of fatty acid and glyceride. Triglycerides are the most high-energy compound, and the adipose tissue, in general, is the energy repository of the organism. Besides the supportive and trophic functions, the adipose tissue is a very good heat insulator that protects the organism from heat loss. Moreover, the adipose tissue participates in the production of heat – fat oxygenation produces heat – synthesis, and accumulation of hormones (estrogen, leptin), as well as accumulation of fat-soluble vitamins (A, D, E, K).
Today, the adipose tissue properties and functions are well studied and actively used in medicine. Thus, for instance, moving adipose tissue from one area to another one (lipolifting, lipotransfer, lipografting) was the most popular procedure in aesthetic medicine in 2016, according to the American Association of Plastic Surgeons.
It should be mentioned that stromal cells, including multipotent mesenchymal stromal cells (MSCs) account for 50% of the adipose tissue. The presence of MSCs in the adipose tissue was first demonstrated by P. Zuk et al. in 2001. In this keystone work, the researches showed high content of MSCs in the adipose tissue obtained by liposuction (2,500 times per a unit of volume as much as in the bone marrow) and the full identity of their properties with those of the bone marrow MSCs (adherence to plastic, expression of cell surface markers and multipotential differentiation). After this publication, the adipose tissue is looked at as the most available source for obtaining stromal cells. However, the adipose tissue also contains some other cell types that can be isolated from the lipoaspirate. They include endothelial, smooth muscle and supra-adventitial vessel cells (the adipose tissue contains a great deal of capillaries, arterioles, and venules), white blood cells (as some blood gets into the lipoaspirate at liposuction), pericytes (cells of mesenchymal origin, surround capillaries), as well as fibroblasts, macrophages and mast cells. All this totality of nucleated cells is called the stromal vascular fraction of the adipose tissue.
With our development, SVF can be obtained by fermentation in a standardized manner. The fermentation is the most popular way to obtain SVF due to the high volume extracted. The method is based on the treatment of lipoaspirate with an enzyme – collagenase that selectively breaks down collagen fibrils – the main component of the adipose tissue stroma. The 30-minute treatment of lipoaspirate with collagenase destroys stroma that holds adipocytes in lobules, adipocyte membranes break down, the fat contained in them gets out and floats to the surface of the solution. It also leads to the release of other stromal cell elements. After fermentation, lipoaspirate is washed from the enzyme and adipocytes degradation products several times, and nucleated cells are precipitated by centriguration. The cell pellet presents the stromal vascular fraction and can be used for the treatment of various diseases or obtaining clean MSCs population by cultivation. It should be mentioned that it takes about two hours to obtain SVF. And the procedure of fermentation itself can be carried out in a sterile disposable closed system right in the operating room.
The mechanism of SVF therapeutic action
The main advantage of adipose tissue as a source of cells is a minimally invasive procedure of adipose tissue cells harvesting – liposuction – which is widely used in aesthetic medicine. The procedure is standardized, easy to perform and can be carried out under local anaesthesia. Nearmedic technology allows for obtaining of SVF as the autologous end-product within 90 minutes after liposuction. The cell fraction is immediately injected to the same patient to recover damaged tissue or organ. Our device carries out step-by-step washing and treatment of the adipose tissue with an enzyme in order to extract stromal vascular fraction, where the adipose tissue (lipoaspirate) is added into the device – a closed sterile tightly sealed disposable container – and all stages of lipoaspirate fermentation and washing are performed in accordance with a well-established protocol. Final stromal vascular fraction is extracted via a relevant channel of the separator. This system can obtain cells that remain viable. The product can be used to treat patients immediately after cells are obtained.
Clinical studies show that SVF can be used almost in every area of medicine: traumatology, urology, gynecology, cardiology, endocrinology, neurology etc. A number of clinical studies to demonstrate efficacy and safety of the method in the treatment of various diseases are conducted in Russia and globally. These key parameters of cell product quality are assessed in accordance with international good practices.
Today, this technology is mostly used in aesthetic medicine to treat various skin damages: post surgical scars, cicatricial tissue, alopecia, pigmentation and age-related changes. Moreover, the technology is used in plastic, reconstructive surgery to enrich the lipoaspirate used to correct soft tissue defects, e.g., to increase the bust or buttock size. In regenerative surgery, SVF has proven to be useful in the treatment of various skin damages (burns, ishaemic ulcers). Studies are conducted regarding the treatment of urogenital diseases and restoration of damaged ligaments and articular cartilages, as well as to increase the efficacy of conventional treatment regimens, improve the quality of life and achieve revitalization. A number of studies have demonstrated the efficacy of SVF use in the treatment of diseases without any effective therapies or with a very limited degree of their effect.
Such products can’t be viewed as a sovereign remedy. However, considering their physiological and personalized origin, we can say that they’ll be effective in the treatment of various diseases when used on the individual bases.
MSCs of adipose tissue are a cell population of SVF and are considered pericytes by some researchers. As we’ve mentioned above, SVF is of a heterogeneous cell composition. Besides MSCs, it contains endothelial cells of varying differentiation degree, smooth muscle cells of blood vessels, fibroblasts, tissue macrophages, white and red blood cells. The ratio between the cell populations is not constant and depends on the method of adipose tissue harvesting, area of harvesting (anatomic localization), age, gender, patients’ medical history, lipoaspirate transportation conditions and shelf life, as well as the method of SVF harvesting. The heterogeneous composition of SVF provides it with a number of advantages over MSCs. Thus, SVF can be used in the period of an active inflammatory response as it contains white blood cells and tissue macrophages. In their turn, MSCs within SVF have a stronger and faster regulating effect on the regenerative processes due to the presence of target cells for cytokines produced by them (endothelial and smooth muscle cells, fibroblasts). One of the key effects associated with SVF injection is neoangiogenesis – formation of microvasculature that ensures adequate histotrophic nutrition. This leads to the antifibrotic effect of SVF. Thus, SVF has a great therapeutic potential and a number of advantages compared to MSCs, and can be obtained right after the liposuction procedure.
MSCs are a separate group of poorly differentiated cells capable of differentiation in vitro into various specialized tissues and cells (adipose, bone, cartilaginous, muscle, nerve etc.). To obtain a cell product consisting of MSCs, it’s necessary to cultivate cells in a specialized laboratory in sterile conditions in compliance with recommendations of professional communities and good practice requirements. The therapeutic potential of MSCs is based on their ability to regulate regeneration processes in tissues using a paracrinal way by producing a wide range of cytokines, growth factors and other biologically active molecules. At that, the mechanisms of neoangiogenesis, stimulation of neural terminals growth, inflammation modulation, apoptosis inhibition, attracting circulating stem cells to the affected area, induction of tissue precursor cells are realized.
Our principal scientific competitors are groups of researches looking at biological properties of the adipose tissue and adipose tissue cell products, SVF specifically. The groups are led by the world’s leading plastic surgeons.
The research group of professor Guy Magalon who is the Head of the Plastic Surgery Department, Hospital de la Conception, Marseilles, France. G. Magalon leads
- the research of SVF biological effects, the optimal fat graft/SVF ratio (in CAL (Cell Assisted Lipotransfer))
- The group develops of the antibody panel to describe SVF subpopulation content
- studies the possibility to simultaneously use SVF and platelet enriched plasma.
G. Magalon’s group of researchers and physicians conducted clinical studies of the SVF use for the treatment of sclerodactylia, conduct clinical studies on the treatment of rectovaginal fistulas and non-clinical studies of the management of stress urinary incontinence and osteoarthritis. Moreover, this research group was the first to suggest the algorithm to assess SVF biological safety. Professor G. Magalan has great expertise in the use of lipofilling and SVF in the aesthetic medicine and has developed the procedure for obtaining and using micro fat.
The project’s team has formed a partnership with G. Magalon’s research team, aimed at the development of approaches to define the subpopulational composition of SVF, protocols for standardized SVF harvesting and at the search of optimal conditions for its clinical application. Wider collaboration is planned as part of the project
Cytori Therapeutics Inc. (The Director General is Mark Hedrick) research group led by J. Fraser, Head of the Science Department, California, the United States. M. Hedrick was the head of the research group, a member of which, P. Zuk was the first to describe MSCs and their characteristics in the adipose tissue. Cytori has created Cytori Celution, an automatic device for obtaining SVF, and launched it in Europe and the U.S. The research team of Cytori Therapeutics Inc. developed the minimum criteria to characterize surface markers of various cell populations of SVF and approaches to their biological properties assessment (based on the CFU test). At present, the main focus of the research group is to extend indications for use of SVF – the company finances clinical studies on the management of
- burns of different etiology
A group of Professor Kotaro Yoshimura from Jichi Medical University, Japan. К. Yoshimura was the first to suggest enriching graft transplants with SVF cells to improve their retention at lipofilling and introduced the term CAL Cell Assisted Lipotransfer. Moreover, in scientific research, K. Yoshimura described the critical size of the adipose tissue granule that can be grafted without SVF. He supervised the development of methodologies for manual (laboratory) SVF harvesting.
A group of scientists led by Professor Norbert Pallua, Aachen University Hospital, the Department of Plastic Surgery, Hand and Burns Surgery, Director. N. Pallua represents Central Europe in the International Confederation of Plastic Reconstructive and Aesthetic Surgery (IPRAS). Since 2001, he’s represented Germany in the European Union of Medical Specialists (UEMS) and has been the chair of the Regulatory Committee for Aesthetic Medicine since 2008. He mainly deals with reconstructive and aesthetic surgery as well as research work. Professor Pallua specializes mainly on the head and neck reconstructive surgery, using the methods he developed to reconstruct the whole face both functionally and aesthetically after removal of tumors or injuries. The majority of surgical techniques developed by N. Pallua are based on the SVF use. N. Pallua developed the procedure for obtaining and use of emulsified fat (nanofat). He supervises a great deal of studies on SVF properties and possibilities of its therapeutic use.
Piter Rubin, M.D., is Chair of the Department of Plastic Surgery and the Professor of Plastic Surgery at the University of Pittsburgh, as well as Professor of Bioengineering. Piter Rubin is an acknowledged expert in the area of research of stem cells obtained from the adipose tissue and reconstructive surgery. Dr. Rubin leads a program for development of novel strategies for the use of the adipose tissue MSCs to address various diseases. He is co-director of the Adipose Stem Cell Center and co-director of the Aesthetic Plastic Surgery Center at the University of Pittsburgh. His team’s research focuses on applications of adult adipose-derived stem cells for restoring damaged tissues after various injuries and anticancer therapy. Currently, he is the principal investigator in clinical trials using technologies designed to improve the lives of wounded military personnel. He’s recently founded and directs the Center for Innovation in Restorative Medicine at the University of Pittsburgh Medical Center.
SVF clinical use
SVF in medical practice was originally used in plastic and reconstructive surgery.
Plastic surgeons have been using lipofilling – obtaining the adipose tissue from one anatomical site and placing it into another site – for over 70 years.
Lipofilling is used to correct soft tissue anatomical defects of various etiologies
and in aesthetic purposes to improve skin condition. However, when large amount of the adipose tissue is transfered, e.g., for breast shape correction, the transplanted fat is eventually reabsorbed or substituted by the connective tissue. In early 2000-s, the research group led by M. Hedrick, a plastic surgeon, first demonstrated the possibility to obtain multipotent mesenchymal stromal cells (MSCs) from the adipose tissue [Zuk P. et al., 2001]. Later, K. Yoshumura, a Japanese plastic surgeon [Yoshimura K. et al., 2008], suggested to enrich the adipose tissue with nucleated cells harvested from this tissue – i.e., with the stromal vascular fraction (cell-assisted lipotransfer – CAL). The authors used an animal model to demonstrate that stromal cells play an important role in the process of fat graft acceptance by ensuring neoangiogenesis and new tissue formation. Lipoaspirate was calculated to contain almost twice as few stromal cells as the intact fat. The authors believed that reconstitution of the natural transplant cell concentration improved acceptance of the injected adipose tissue as compared to the non-enriched lipoaspirate, which was proven in experiment in mice and by individual clinical cases [Yoshimura K. et al., 2008]. According to Zhu et al., it takes 3 to 7 days to form the capillary network when enriched lipografts are used [Zhu M. et al., 2010].
The use of CAL has enabled plastic surgeons to take lipofilling to a principal new level – they have started to use the enriched adipose tissue
- for severe defect reconstruction
- in the treatment of cicatricial deformities
- in oncoplastic breast reconstruction [Rigotti G. et al., 2012].
Thus, according to the American Society of Plastic Surgeons, lipofilling was one of the most popular plastic surgeries in the U.S. in 2016. However, there are a lot of other ways to use SVF in clinical practice. This is due to a number of effects produced by various SVF cell populations when injected into tissues:
- synthesis of growth factors
- synthesis of cytokines
- synthesis of extracellular matrix components,
- which enables neoangiogenesis stimulation,
- modulation of immune response and inflammation,
- keeping differentiated cells in the abnormal focus viable,
- remodeling of pathologically changed tissue,
- induction of differentiation into specialized cells of mesenchymal origin.
All these universal effects enable the use of SVF almost in every area of medicine
- trauma care
- neurology etc.
both locally and systemically as intravenous injections. Currently, researchers study regeneration of bone, cartilage, muscle, and nerve tissue with the adipose tissue SVF, which is one of the most popular tools of regenerative medicine (Y. Illouz et al., 2011). Much research looks at the use of the adipose tissue SVF in the treatment of
- acute graft-versus-host reaction
- chronic autoimmune thrombocytopenic purpura
- rheumatoid arthritis
- Crohn’s disease and other diseases (B. Fang et al., 2006, B. Fang et al., 2009, H. Trivedi et al., 2008, D. Garcia-Olmo et al., 2003, T. Ichim et al., 2010).
Current Clinical Studies
The list of clinical studies registered in the ClinicalTrials.gov database obtained at the query “stromal vascular fraction” as of April 5, 2017:
|1||Recruiting||The Improving Effect of Autologous Stromal Vascular Fraction (SVF) in Adipose Tissue on Skin Grafting||NCT02546882||Shanghai Jiao Tong University School of Medicine||https://clinicaltrials.gov/ct2/show/NCT0 2546882?term=NCT02546882&rank=1|
|2||Not yet recruiting||Stromal Vascular Fraction for Treatment of Xerostomia||NCT03061110||Midwestern Regional Medical Center||https://clinicaltrials.gov/ct2/show/NCT0 3061110?term=NCT03061110&rank=1|
|3||Recruiting||Subcutaneous Injection of Autologous Adipose Tissue-derived Stromal Vascular Fraction Into the Fingers of Patients With Systemic Sclerosis||NCT02558543||Assistance Publique Hopitaux De Marseille||https://clinicaltrials.gov/ct2/show/NCT0 2558543?term=NCT02558543&rank=1|
|4||Active, not recruiting||Treatment of Osteoarthritis With the Stromal Vascular Fraction of Abdominal Adipose Tissue – a Pilot Study||NCT02697682||Kristoffer Barfod, Hvidovre University Hospital||https://clinicaltrials.gov/ct2/show/NCT0 2697682?term=NCT02697682&rank=1|
|5||Completed||Comparison Between Celution Preparation and Manual Preparation of Adipocyte Derived Regenerative Cells, Using Stromal Vascular Fraction Cell Counts (COMPARE)||NCT01127230||Novena Medical Center||https://clinicaltrials.gov/ct2/show/NCT0 1127230?term=NCT01127230&rank=1|
|6||Recruiting||Innovative Treatment for Scarred Vocal Cords by Local Injection of Autologous Stromal Vascular Fraction||NCT02622464||Assistance Publique Hopitaux De Marseille||https://clinicaltrials.gov/ct2/show/NCT0 2622464?term=NCT02622464&rank=1|
|7||Recruiting||ADMSCs for the Treatment of Systemic Sclerosis||NCT02975960||The Catholic University of Korea||https://clinicaltrials.gov/ct2/show/NCT0 2975960?term=NCT02975960&rank=1|
|8||Unknown||To Evaluate the Safety and Efficacy of IM and IV Administration of Autologous ADMSCs for Treatment of CLI||NCT02145897||Kasiak Research Pvt. Ltd.||https://clinicaltrials.gov/ct2/show/NCT0 2145897?term=NCT02145897&rank=1|
|9||Recruiting||Adipose-Derived Cellular Stromal Vascular Fraction in Autoimmune, Inflammatory, Neurologic Conditions||NCT02939859||Healeon Medical Inc||https://clinicaltrials.gov/ct2/show/NCT0 2939859?term=NCT02939859&rank=1|
|10||Active, not recruiting||Injection of Autologous Adiposederived Stromal Vascular Fraction in the Finger of Systemic Sclerosis Patients||NCT03060551||Suk-Ho Moon, Seoul St. Mary’s Hospital||https://clinicaltrials.gov/ct2/show/NCT03060551?term=NCT03060551&rank=1|
|11||Completed||Assessment of the Subcutaneous Reinjection of Human Autologous Adipose-derived||NCT01813279||Assistance Publique Hopitaux De Marseille||https://clinicaltrials.gov/ct2/show/NCT01813279?term=stromal+vascular+fraction&rank=14|
|12||Completed Has Results||Immunophenotyping of Fresh Stromal Vascular Fraction From Adipose Derived Stem Cells (ADSC) Enriched Fat Grafts||NCT01771913||Luiz Alexandre Lorico Tissiani, University of Sao Paulo||https://clinicaltrials.gov/ct2/show/record/ NCT01771913?term=stromal+vascular+ fraction&rank=15|
|13||Recruiting||An Innovative Treatment for Fistulain-ano in Crohn Disease : Local Micro Reinjection of Autologous Fat and SVF||NCT02520843||Assistance Publique Hopitaux De Marseille||https://clinicaltrials.gov/ct2/show/record/ NCT02520843?term=stromal+vascular+ fraction&rank=16|
|14||Recruiting||Treatment of Chronic Leg Ulcers With Autologous Stromal Vascular Fraction||NCT02987101||Navid Toyserkani, Odense University Hospital||https://clinicaltrials.gov/ct2/show/NCT0 2987101?term=stromal+vascular+fractio n&rank=17|
|15||Recruiting||Autologous Adipose-Derived Stromal Vascular Fraction Cells for Osteoarthritis Treatment||NCT02967874||Russian Academy of Medical Sciences||https://clinicaltrials.gov/ct2/show/NCT0 2967874?term=stromal+vascular+fractio n&rank=18|
|16||Completed||Extraction of Stromal Vascular Fraction and Stem Cells From Fat Tissue||NCT01399307|| United States, Pennsylvania
Blair Plastic Surgery
Altoona, Pennsylvania, United States, 16602
Indiana Regional Medical Center
Indiana, Pennsylvania, United States, 15701
Sponsors and Collaborators
Investigators Principal Investigator: Shahram
Rahimian, MD Antria
|https://clinicaltrials.gov/ct2/show/study/ NCT01399307?term=stromal+vascular+ fraction&rank=19|
|17||Unknown||Evaluate Safety and Efficacy of Intravenous Autologous ADMSc for Treatment of Idiopathic Pulmonary Fibrosis||NCT02135380||Kasiak Research Pvt. Ltd.||https://clinicaltrials.gov/ct2/show/NCT0 2135380?term=stromal+vascular+fractio n&rank=20|
|18||Completed||Use of Autologous Adipose-Derived Stromal Vascular Fraction to Treat Osteoarthritis of the Knee||NCT02276833||Renew Center, San Antonio, Texas||https://clinicaltrials.gov/ct2/show/record/ NCT02276833?term=stromal+vascular+ fraction&rank=21|
|19||Recruiting||Adipose Derived Stem Cells in Facial Fat Grafting (SVF)||NCT02526576||United States, Pennsylvania Delmont Surgery Center Recruiting||https://clinicaltrials.gov/ct2/show/study/ NCT02526576?term=stromal+vascular+ fraction&rank=22|
|20||Recruiting||Study to Assess the Safety and Effects of Autologous AdiposeDerived Stromal Cells in Patients With Alzheimer’s Disease||NCT02912169||Ageless Regenerative Institute||https://clinicaltrials.gov/ct2/show/NCT0 2912169?term=stromal+vascular+fractio n&rank=23|
|21||Recruiting||Grafting of Autologous Adipose Stromal Cell Trial (GAASC)||NCT02116933||Cedars-Sinai Medical Center||https://clinicaltrials.gov/ct2/show/study/ NCT02116933?term=stromal+vascular+ fraction&rank=24|
|22||Recruiting||Point-of-Care Adipose-derived Cells for Hair Growth (ASVF-2016)||NCT02729415||University of Florida||https://clinicaltrials.gov/ct2/show/study/ NCT02729415?term=stromal+vascular+ fraction&rank=25|
|23||Unknown||Effect of SVF Derived MSC in DCD Renal Transplantation||NCT02492490||Fuzhou General Hospital||https://clinicaltrials.gov/ct2/show/NCT0 2492490?term=stromal+vascular+fractio n&rank=26|
|24||Not yet recruiting||SCLERoderma et Adipose-DErived Stroma Cells (SCLERADECIII)||NCT02866552||Publicique Hopitaux de Marseille||https://clinicaltrials.gov/ct2/show/NCT0 2866552?term=stromal+vascular+fractio n&rank=27|
|25||Recruiting||Safety and Efficacy of Autologous SVF Cells in Treating Patients With Osteoarthritis||NCT02846675||Yin Feng, Shanghai East Hospital||https://clinicaltrials.gov/ct2/show/NCT0 2846675?term=stromal+vascular+fractio n&rank=28|
|26||Recruiting||Adipose-derived SVF for the Treatment of Knee OA||NCT02726945||The GID Group
Locations United States, New Jersey
Cooper University Hospital
|https://clinicaltrials.gov/ct2/show/NCT0 2726945?term=stromal+vascular+fractio n&rank=29|
|27||Unknown||Stromal Vascular Fraction (SVF) for Treatment of Recto-vaginal Fistula (HULPCIR)||NCT01548092||Instituto de Investigación Hospital Universitario La Paz||https://clinicaltrials.gov/ct2/show/study/ NCT01548092?term=stromal+vascular+ fraction&rank=30|
|28||Unknown||Stromal Vascular Fraction (SVF) for Treatment of Enterocutaneous Fistula (HULPUTC) (HULPUTC)||NCT01584713||Instituto de Investigación Hospital Universitario La Paz||https://clinicaltrials.gov/ct2/show/study/ NCT01584713?term=stromal+vascular+ fraction&rank=31|
|29||Completed||Safety Study of Antria Cell Preparation Process to Enhance Facial Fat Grafting With Adipose Derived Stem Cells||NCT01828723||United States, Antria||https://clinicaltrials.gov/ct2/show/record/ NCT01828723?term=stromal+vascular+ fraction&rank=32|
|30||Unknown||Safety and Efficacy of Autologous Adipose-Derived Stem Cell Transplantation in Type 2 Diabetics||NCT00703612||Adistem Ltd||https://clinicaltrials.gov/ct2/show/NCT0 0703612?term=stromal+vascular+fractio n&rank=33|
|31||Unknown||Safety and Efficacy of Autologous Adipose-Derived Stem Cell Transplantation in Patients With Type 1 Diabetes||NCT00703599||Adistem Ltd||https://clinicaltrials.gov/ct2/show/NCT0 0703599?term=stromal+vascular+fractio n&rank=34|
|32||Recruiting||Safety of Adipose-Derived Stem Cell Stromal Vascular Fraction||NCT02590042||AdiSave Inc.||https://clinicaltrials.gov/ct2/show/NCT0 2590042?term=stromal+vascular+fraction&rank=35|
|33||Recruiting||Outcomes Data of Adipose Stem Cells to Treat Multiple Sclerosis||NCT02157064||StemGenex||https://clinicaltrials.gov/ct2/show/study/ NCT02157064?term=stromal+vascular+ fraction&rank=36|
|34||Recruiting||Biocellular-Cellular Regenerative Treatment Scaring Alopecia and Alopecia Areata (SAAA)||NCT03078686||Robert W Alexander, MD, Regeneris Medical||https://clinicaltrials.gov/ct2/show/NCT0 3078686?term=stromal+vascular+fractio n&rank=37|
|35||Recruiting||Outcomes Data of Adipose Stem Cells to Treat Osteoarthritis||NCT02241408||StemGenex,La Jolla, California, United States, 92037||https://clinicaltrials.gov/ct2/show/record/ NCT02241408?term=stromal+vascular+ fraction&rank=38|
|36||Recruiting||Safety and Effects of Autologous Adipose-Derived Stromal Cells Delivered in Patients With Type II Diabetes||NCT01453751||Ageless Regenerative Institute||https://clinicaltrials.gov/ct2/show/NCT0 1453751?term=stromal+vascular+fractio n&rank=39|
|37||Recruiting||Outcomes Data of Adipose Stem Cells to Treat Rheumatoid Arthritis||NCT02348086||StemGenex, La Jolla, California, United States, 92037||https://clinicaltrials.gov/ct2/show/study/ NCT02348086?term=stromal+vascular+ fraction&rank=40|
|38||Recruiting||Outcomes Data of Adipose Stem Cells to Treat Chronic Obstructive Pulmonary Disease||NCT02348060||StemGenex, La Jolla, California, United States, 92037||https://clinicaltrials.gov/ct2/show/record/ NCT02348060?term=stromal+vascular+fraction&rank=41|
|39||Recruiting||Evaluation of the Tissue Genesis® Icellator Cell Isolation System™ to Treat Critical Limb Ischemia (CLI-DI)||NCT02234778|| Indiana University
|https://clinicaltrials.gov/ct2/show/NCT0 2234778?term=stromal+vascular+fractio n&rank=42|
|40||Recruiting||AGA Biocellular Stem/Stromal Hair Regenerative Study (STRAAND)||NCT02849470||Robert W. Alexander, MD, FICS, Healeon Medical Inc||https://clinicaltrials.gov/ct2/show/NCT0 2849470?term=stromal+vascular+fractio n&rank=43|
|41||Completed||Autologous Adipose Stem Cells and Platelet Rich Plasma Therapy for Patients With Knee Osteoarthritis||NCT02142842||Phuc Van Pham, University of Science Ho Chi Minh City||https://clinicaltrials.gov/ct2/show/record/ NCT02142842?term=stromal+vascular+ fraction&rank=44|
|42||Recruiting||Cellular & Biocellular Regenerative Therapy in Musculoskeletal Pain, Dysfunction,Degenerative or Inflammatory Disease (BRT)||NCT03090672||Regeneris Medical North Attleboro, Massachusetts, United States||https://clinicaltrials.gov/ct2/show/NCT0 3090672?term=stromal+vascular+fractio n&rank=45|
|43||Recruiting||Autologous Adipose-Derived Stromal Cells Delivered Into the Corpus Cavernous in Patients With Erectile Dysfunction||NCT02087397||Ageless Regenerative Institute||https://clinicaltrials.gov/ct2/show/NCT0 2087397?term=stromal+vascular+fractio n&rank=46|
|44||Recruiting||Use of Adipose-Derived Stem/Stromal Cells in Concussion and Traumatic Brain Injuries (C-TBI)||NCT02959294|| Robert W. Alexander,
MD, FICS, Healeon
|https://clinicaltrials.gov/ct2/show/NCT0 2959294?term=stromal+vascular+fractio n&rank=47|
|45||Terminate d||Safety and Efficacy of Adipose Derived Stem Cells in Refractory Rheumatoid Arthritis, Systemic Lupus Erythematosus or Sharp’s Syndrome||NCT02741362||Arkansas Heart Hospital||https://clinicaltrials.gov/ct2/show/record/ NCT02741362?term=stromal+vascular+ fraction&rank=48|
|46||Recruiting||Autologous Adipose-Derived Stromal Cells Delivered Intra-articularly in Patients With Osteoarthritis.||NCT01739504||Ageless Regenerative Institute||https://clinicaltrials.gov/ct2/show/NCT0 1739504?term=stromal+vascular+fractio n&rank=49|
|47||Recruiting||Safety and Clinical Outcomes Study: SVF Deployment for Orthopedic, Neurologic, Urologic, and Cardio-pulmonary Conditions||NCT01953523||Elliot Lander, Cell Surgical Network Inc.||https://clinicaltrials.gov/ct2/show/NCT0 1953523?term=stromal+vascular+fractio n&rank=50|
|48||Active, not recruiting||Adipose-derived SVF for Treatment of Alopecia||NCT02626780||Maxwell AestheticsNashville, Tennessee, United States||https://clinicaltrials.gov/ct2/show/record/ NCT02626780?term=stromal+vascular+ fraction&rank=51|
|49||Recruiting||Induction With SVF Derived MSC in Living-related Kidney Transplantation||NCT02492308||Fuzhou General Hospital Fuzhou, Fujian, China||https://clinicaltrials.gov/ct2/show/NCT0 2492308?term=stromal+vascular+fractio n&rank=52|
|50||Recruiting||Adipose Derived Stem Cells Transplantation for Chronic Obstructive Pulmonary Disease||NCT02645305||Phuc Van Pham, University of Science Ho Chi Minh City||https://clinicaltrials.gov/ct2/show/record/ NCT02645305?term=stromal+vascular+ fraction&rank=53|
|51||Recruiting||Safety and Efficacy of Adipose Derived Stem Cells for Chronic Obstructive Pulmonary Disease||NCT01559051||Ageless Regenerative Institute||https://clinicaltrials.gov/ct2/show/NCT0 1559051?term=stromal+vascular+fractio n&rank=54|
|52||Active, not recruiting||Treatment of Breast Cancer Related Lymphedema With Cell-assisted Lipotransfer||NCT02592213||Navid Toyserkani, Odense University Hospital||https://clinicaltrials.gov/ct2/show/NCT0 2592213?term=stromal+vascular+fractio n&rank=55|
|53||Recruiting||Adipose Stem/Stromal Cells in RSD, CRPS, Fibromyalgia (ADcSVF-CRPS)||NCT02987855||Robert W. Alexander, MD, FICS, Healeon Medical Inc||https://clinicaltrials.gov/ct2/show/NCT0 2987855?term=stromal+vascular+fractio n&rank=56|
|54||Not yet recruiting||Healing Chronic Venous Stasis Wounds With Autologous Cell Therapy||NCT02961699||InGeneron, Inc.||https://clinicaltrials.gov/ct2/show/NCT0 2961699?term=stromal+vascular+fractio n&rank=57|
|55||Unknown||Adipose Derived Regenerative Cellular Therapy of Chronic Wounds||NCT02092870||Tower Outpatient Surgical Center||https://clinicaltrials.gov/ct2/show/NCT0 2092870?term=stromal+vascular+fractio n&rank=58|
|56||Recruiting||Safety and Preliminary Efficacy of Adipose Derived Stem Cells and Low Frequency Ultrasound in Peripheral Arterial Disease||NCT02756884||Arkansas Heart Hospital||https://clinicaltrials.gov/ct2/show/record/ NCT02756884?term=stromal+vascular+ fraction&rank=59|
|57||Recruiting||Safety, Tolerability and Preliminary Efficacy of Adipose Derived Stem Cells for Patients With Chronic Obstructive Pulmonary Disease||NCT02161744||Arkansas Heart Hospital||https://clinicaltrials.gov/ct2/show/NCT0 2161744?term=stromal+vascular+fractio n&rank=60|
|58||Recruiting||Amp 30: Autologous Fat Grafting, Amputation Sites Pain: Randomized (Amp 30)||NCT02076022||J. Peter Rubin, MD, University of Pittsburgh||https://clinicaltrials.gov/ct2/show/NCT0 2076022?term=stromal+vascular+fractio n&rank=61|
|59||Completed||Intra-articular Injection in the Knee of Adipose Derived Stromal Cells and Platelet Rich Plasma for Osteoarthritis||NCT03089762||Bioheart, Inc||https://clinicaltrials.gov/ct2/show/NCT0 3089762?term=stromal+vascular+fractio n&rank=62|
|60||Completed Has Results||ADSC Injections for Pain Management of Osteoarthritis in the Human Knee Joint||NCT02357485||Collaborator: Plastic Surgery Education and Research Foundation||https://clinicaltrials.gov/ct2/show/NCT0 2357485?term=stromal+vascular+fractio n&rank=63|
|61||Unknown||Safety and Clinical Effectiveness of A3 SVF in Osteoarthritis||NCT01947348||barbara krutchkoff, Institute of Regenerative and Cellular Medicine||https://clinicaltrials.gov/ct2/show/NCT0 1947348?term=stromal+vascular+fractio n&rank=64|
|62||Recruiting||Use of Autologous Adipose-Derived Stem/Stromal Cells (AD-cSVF) in Symptomatic Benign Prostate Hypertrophy (SVF-BPN)||NCT02961114||Robert W. Alexander, MD, FICS, Healeon Medical Inc||https://clinicaltrials.gov/ct2/show/NCT0 2961114?term=stromal+vascular+fraction&rank=65|
|63||Not yet recruiting||Pilot Study of Skin Quality Improvement After Adipose-drived Stem Cell Transfer in Irradiated Breasts||NCT01801878||Seoul National University Hospital||https://clinicaltrials.gov/ct2/show/NCT0 1801878?term=stromal+vascular+fractio n&rank=66|
|64||Recruiting||Outcomes Data of Adipose Stem Cells to Treat Parkinson’s Disease||NCT02184546||StemGenex||https://clinicaltrials.gov/ct2/show/NCT0 2184546?term=stromal+vascular+fractio n&rank=67|
|65||Recruiting||Study to Assess the Safety and Effects of Autologous Adipose-Derived Stromal Cells Delivered Into Patients With Multiple Sclerosis||NCT01453764||Ageless Regenerative Institute||https://clinicaltrials.gov/ct2/show/NCT0 1453764?term=stromal+vascular+fractio n&rank=68|
|66||Recruiting||Clinical Outcomes of Open Wedge High Tibial Osteotomy With Autologous Bone Marrow or Adipose-derived Stem Cell Therapy (HTOSC)||NCT02642848||Dongsik Chae, Catholic Kwandong University||https://clinicaltrials.gov/ct2/show/NCT0 2642848?term=stromal+vascular+fractio n&rank=69|
|67||Terminate d||Effectiveness of Adipose Tissue Derived Mesenchymal Stem Cells as Osteogenic Component in Composite Grafts (ROBUST)||NCT01532076||University Hospital, Basel, Switzerland||https://clinicaltrials.gov/ct2/show/NCT0 1532076?term=stromal+vascular+fractio n&rank=70|
|68||Recruiting||Use of Autologous, Adult Adipose-Derived Stem/Stromal Cells in Inflammatory Bowel Disease (ADcSVF-IBD)||NCT02952131||Robert W. Alexander, MD, FICS, Healeon Medical Inc||https://clinicaltrials.gov/ct2/show/NCT0 2952131?term=stromal+vascular+fractio n&rank=71|
|69||Recruiting||Use of Autologous, Adult Adipose-Derived Stem/Stromal Cells In Chronic Lung Disorders (ADcSVF-COPD)||NCT02946658||Robert W. Alexander, MD, FICS, Healeon Medical Inc||https://clinicaltrials.gov/ct2/show/NCT0 2946658?term=stromal+vascular+fractio n&rank=72|
|70||Recruiting||Leipzig Adipose Tissue Childhood Cohort (LeipAT Child)||NCT02208141||Antje Koerner, Prof. Dr. med., University of Leipzig||https://clinicaltrials.gov/ct2/show/NCT0 2208141?term=stromal+vascular+fractio n&rank=73|
Scientific Research on the Project
In spite of clear mechanisms and proven efficacy and safety of the SVF clinical use, full understanding of the specific cell subpopulations forming SVF is still not achieved. The quantitative and qualitative composition of SVF, its immunophenotype and possible direction of cell differentiation have not been described in detail so far. Detailed study of SVF functional properties is required to fully understand the mechanisms of therapeutic action and is a prerequisite to introduce this product into a wider clinical practice and to extend its indications.
As part of the project implementation, research aimed at the in-depth studying of SVF subpopulational composition by 25 surface markers and the analysis of gene expression profiles in stromal cells are planned. Experimental results will enable description of phenotypes of all nucleated cells subpopulations forming SVF, including intermediary (transitory) forms. These data will serve as a basis for the creation of the hierarchy of the fat compartment (dipherone) cells, which is necessary to identify the differentiation path of cells and to describe the true cambial pool of cells, responsible for the regeneration and maintaining stable cell composition in the perivascular niche of the adipose tissue.
Summarized results will help to provide a comprehensive picture of therapeutic SVF mechanisms of action and to identify strategies for the therapeutic use of this cell product for the first time.
Moreover, the adipose tissue can be considered for the use in rehabilitation medicine and health-preserving techniques.
The project participants have their own unique developments in lipoaspirate cryopreservation and long storage technology. The technology is protected by two RF patents. The procedure developed allows preserving the adipose tissue for indefinite time without loss of its properties. Within 90 minutes after defrosting, the adipose tissue sample can be prepared for the use as a filler or for obtaining the cell product – SVF. Cryopreservation of the adipose tissue will be developed into a separate supplementary service in the project’s portfolio. Therefore, the present project is interesting not just for the applied medical science, but also regarding its contribution to the industry’s comprehensive development, including in the industrial and economic aspects.