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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

  • osteoarthritis
  • burns of different etiology
  • sclerodermia.

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

  • displasias
  • posttraumatic
  • postoperative

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
  • urology
  • gynecology
  • cardiology
  • endocrinology
  • 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:

Статус Название Организация Ссылка
 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 Adipose￾derived 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 Fistula￾in-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

Antria

Investigators Principal Investigator: Shahram

Rahimian, MD Antria

More Information

 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 Adipose￾Derived 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
Hospital
 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
Medical Inc
 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.