MiniTC Adipose System Now Faster, More Convenient, Personalized
New syringes and a choice of cannulas will make adipose processing faster and personalized to each physician’s needs.
CHICAGO/April 4, 2023 – Jointechlabs, Inc., a privately held US-based regenerative medicine and therapeutics company, today announced upgraded syringes and cannulas that ship with the acclaimed MiniTC and Mini-Stem Adipose Processing systems.
The syringe upgrade provides faster and more efficient harvesting and precise input into and output from the MiniTC device. Additionally, it is FDA-cleared for lipoaspiration.
The additional cannula (lipoaspirate harvester) allows for faster harvesting, yet preserves the high yield ratio of the MiniTC grafting protocol. This second cannula provides the physician with a choice of cannulas based on personal preference.
“Many physicians have said that MiniTC’s current, Sorenson-style cannula is their choice for adipose harvesting, in particular for fibrous and/or lean adipose tissue,” said Dr. Nathan Katz, Jointechlabs CEO. “But others have told us they prefer a faster cannula that reduces harvesting time. By providing a choice with every MiniTC, physicians can now choose the cannula they prefer for virtually any type of patient body structure.”
Dr. Ariana DeMers, Orthopedic Surgeon at Restore Orthobiologic, says “One of my favorite parts of MiniTC is the harvester. It’s probably the best one on the market.”
This upgrade is effective immediately. Any physician with existing inventory who would like the new syringes and cannula can contact the company at https://jointechlabs.com/contact.
Privately-held Jointechlabs is an emerging worldwide leader in point-of-care regenerative medicine. Jointechlabs enables healthcare practitioners and hospitals to provide safe, cost-effective, non-surgical regenerative medicine therapies at the point-of-care without change in infrastructure. FDA-cleared MiniTC® for the US market is a stand-alone device for processing autologous fat into regenerative-cell-rich microfat for a variety of orthopedic, aesthetic, wound healing, and reconstructive surgery applications. Outside the US, CE-Mark-pending Mini-Stem System® prepares Microfat and also extracts Stromal Vascular Fraction. Pipeline products include stem-cell therapeutics such as Bioprinting and injectable stem cell scaffolding. More information at www.jointechlabs.com
MDSAP Quality Certification Awarded to Jointechlabs
Medical Device Single Audit Program (MDSAP) certification applies to the United States, Canada, Australia, Brazil, and Japan.
CHICAGO/March 15, 2023 – Jointechlabs, Inc., a privately held US-based regenerative medicine and therapeutics company, today announced it has been granted an MDSAP certification for its quality management system that satisfies the requirements of multiple regulatory jurisdictions. These jurisdictions include the United States, Canada, Australia, Brazil, and Japan.
The MDSAP allows medical device manufacturers to be audited once for compliance with multiple jurisdictions’ standards and regulatory requirements. The program’s main mission is to “…jointly leverage regulatory resources to manage an efficient, effective, and sustainable single audit program focused on the oversight of medical device manufacturers.”
To earn this certification, Jointechlabs underwent a comprehensive audit by a regulatory body. The company demonstrated that its quality management and manufacturing systems conform to the exacting standards of ISO 13485:2016. ISO 13485:2016 is the most recent and rigorous 13485 standard for medical device manufacturers. The requirements cover quality systems, management, and the entire medical device product journey from conceptualization to implementation. Additionally, customer support, event reporting, continuous improvement, and regular product evaluation are components.
“We are thrilled and honored to earn this MDSAP quality certification,” said Dr. Nishit Pancholi, COO of Jointechlabs. “Quality is a core company value and one of the things that set us apart. Moreover, producing the purest, highest quality biologics allows our customers to achieve the best outcome at the lowest risk.”
The MDSAP certification is not mandatory for medical device manufacturers. There is no publicly available listing of companies who are MDSAP certified. However, companies who earn the certification generally make their status known.
European focus includes a new subsidiary in Austria, a medical research center in partnership with a prominent health center, and development and distribution agreements for Germany, Austria, Switzerland, Italy, Spain, and the Balkans.
CHICAGO, OCT. 20, 2022/PRNewswire/–Jointechlabs, Inc., a Regenerative Medicine Solutions company announced a Vienna-based subsidiary named JointechPlus GmbH. They also announced research, development, and clinical partnerships with Laakirchner Gesundheitszentrum (LGZ), a multispecialty health center in Upper Austria, and Educell, a Slovenian biotech company. New distribution partners include R.E.N.G. GmbH and Eywa S.r.l., while a new grant has been secured from the Slovenian government.
“JointechPlus (http://www.jointechplus.at/) allows us to develop and market products for and in cooperation with the European community,” said Dr. Nathan Katz, CEO of Jointechlabs. “We are thrilled to welcome our European partners and investors in our drive to bring regenerative medicine solutions to Europe and the world,” said Dr. Nishit Pancholi, COO of Jointechlabs.
Research, Development, and Clinical Partnerships
JointechPlus has formed a partnership with LGZ (https://www.lgz.co.at/) to establish a medical research center that will be the hub for regenerative medicine solutions, focusing on orthopedic and wound healing therapeutic biologics.
Mr. Christian F. Albrecht, Managing Director at LGZ, said “Our partnership with JointechPlus allows us to bring advanced regenerative medicine solutions to our patients, while expanding our ability to educate and train medical professionals in this fast-growing field.”
Slovenia-based Educell (https:/www.educell.si/en/) has expertise in adipose-derived stem cells, and an extensive clinical network in the Balkans. The partnership has secured a grant from the Slovenian government, positioning Jointechlabs and Educell to be the leaders in point-of-care adipose-based solutions in the Balkans.
The distribution agreements focus on Jointechlabs’ adipose processing systems MiniTC® and Mini-Stem System®. The R.E.N.G. GmbH agreement covers Germany, Austria, and Switzerland, while the agreement with Eywa S.r.l. covers Italy and Spain.
Headquartered in Chicago, IL, privately-held Jointechlabs is an emerging worldwide leader in regenerative medicine, enabling healthcare practitioners to provide safe, cost-effective, non-surgical regenerative medicine therapies at the point of care without change in infrastructure.
FDA-cleared MiniTC® is a stand-alone device for processing autologous fat into regenerative-cell-rich Microfat for a variety of orthopedic, aesthetic, wound healing, and reconstructive surgery applications. Outside the US, CE-Mark-pending Mini-Stem System® extracts Microfat and Stromal Vascular Fraction.
The pipeline includes the development of stem-cell-based therapeutics with 3D Bioprinted constructs and injectable stem-cell scaffolding.
Chicago, Ill, October 3, 2022/ — Jointechlabs, a global leader in point-of-care regenerative medicine, was issued US Patent No. 11,447,748, “Encapsulated Adipose-Derived Stem Cells, Methods for Preparation and Therapeutic Use,” the third utility patent in a family of patents, securing the intellectual property portfolio towards planned development steps.
Jointechlabs’ unique technology is designed to enable health practitioners worldwide to utilize autologous adipose tissue and its derivates (a person’s own fat) for joint pain relief and a wide variety of orthopedic, aesthetic, wound healing, and reconstructive surgery applications.
“Innovation is a cornerstone of our success and strategy as a pioneer and leader of the regenerative medicine industry,” said Dr. Nathan Katz, CEO of Jointechlabs. “This patent strengths the IP basis of our therapeutic development leveraging the already commercially available MiniTC® and Mini-Stem System® platform family. Securing a solid IP portfolio demonstrates both our commitment to innovation and our ability to secure patent protection in a way that strengthens our leadership and our competitive advantage.”
This latest patent covers methods and systems of encapsulating mesenchymal stem cells in a three-dimensional biocompatible gel matrix, maintaining the viability and location of the stem cells for an extended period, a significant advantage for therapeutic treatment efficacy as compared to stem cells in suspension.
Jointechlabs has a portfolio of 12 US and foreign patents. The latest patent joins the family that includes US Patent Nos 9,931,445, 9,938,501, and 10,745,666, issued between 2018 and 2020, with 11,447,748 extending coverage through 2032. Other patents have been granted in China, EU, Israel, Japan, and Ukraine.
Dr. Nishit Pancholi, COO of Jointechlabs added “We are gratified to have earned this latest patent, further memorializing our innovation, which continues to be validated by the global marketplace success of our products.”
Headquartered in Chicago, IL, privately-held Jointechlabs is an emerging worldwide leader in point-of-care regenerative medicine, enabling healthcare practitioners and hospitals provide safe, cost-effective, non-surgical regenerative medicine therapies at the point-of-care without change in infrastructure. FDA-cleared MiniTC® for the US market is a stand-alone device for processing autologous fat into regenerative-cell-rich Microfat for a variety of orthopedic, aesthetic, wound healing, and reconstructive surgery applications. Outside the US, CE-Mark-pending Mini-Stem System® prepares Microfat and also extracts Stromal Vascular Fraction. Pipeline products include stem-cell therapeutics such as Bioprinting and injectable stem cell scaffolding. More information at www.jointechlabs.com and www.linkedin.com/company/jointechlabs. Contact: firstname.lastname@example.org.
Jointechlabs’ MiniTC Training by Dr. Nathan Katz, Ph.D., and Dr. Enrico Guarino
Jointechlabs is an emerging leader in the field of outpatient autologous regenerative and rejuvenating therapies.
The recent commercial launch of the MiniTC® device is causing disruptive waves across the industry. This unique sleekly designed disposable and multifunctional product offers uncomparable simplicity, convenience, and quality altogether.
Jointechlabs genuinely integrates its technology into the existing workflows of healthcare providers, expanding treatment options and bringing the next generation of therapeutics down to everyday medical practice for the whole benefit of patients and communities.
Here is one of the most recent pieces of training for the application of MiniTC-manufactured microfat grafts in the Chicago area.
Guided Lymphangiogenesis for the Treatment of Lymphedema: Preliminary Clinical Results
Catarina Hadamitzky, Tatiana S. Zaitseva, Nathan Katz, Claire P Edelstein, Manuel T. Escarraman, Dung Nguyen, Michael V. Paukshto
Clinic of Plastic, Aesthetic and Hand Surgery, Helios Clinic, Hildesheim, Germany.
Fibralign Corporation, Union City, California, USA.
JointechLabs, Inc, N. Barrington, Illinois, USA.
Instituto Oncológico Dr. Heriberto Pieter, Santo Domingo, Dominican Republic.
Department of Plastic Surgery, Stanford University, Stanford, California, USA.
To address the limitations of current treatments for secondary lymphedema, our study group developed an experimental surgical procedure based on Autologous Lymph Node Fragment (ALNF) transfer supplemented by nanofibrillar collagen scaffold with and without autologous Adipose-Derived Stromal Cells out from the stromal vascular fraction (ADSCs). The efficacy of this scaffold was demonstrated before in a porcine model of secondary lymphedema. To address the challenges of poor survival and low migration from the injection site described in clinical studies of ADSCs, we used ADSC-seeded scaffolds to deliver the cells. These scaffolds seem to support cell survival, maintenance, and function at the targeted site. The ongoing pilot study has 12 patients currently enrolled. We used non-vascularized autologous lymph node fragment transfer (LNFT) as a basic treatment for all patients. It was supplemented by implantation of: BioBridge scaffolds (n=5); BioBridge scaffolds with ADSCs (n=2); BioBridge scaffolds with injected ADSCs (n=1); and injected ADSCs only (n=4; control group still ongoing). In the therapy groups, no complications have been reported after almost one year. 6 of 8 patients using BioBridge responded to the treatment after 6 months with an average volume reduction of about 20%. Two of these patients have attained a normal limb volume ratio (≤1.1) at 3 months after surgery. The average edema reduction in the control group (n=4) was only 1.1% 4 months after surgery. More data will be presented at the time of the conference. While vascularized lymph node transfer is considered to be a more advanced technique than ALNF transfer, there is a great interest in developing countries to have simpler surgery to manage lymphedema without the need for a microscope. On the other hand, the concept of guiding lymphangiogenesis with collagen scaffolds could also potentially improve the efficiency of well-established vascularized lymph node procedures.
3D Bioprinting of Autologous Adipose Tissue for Wound Healing
Critical skin wounds are a major cost for the health sector and lead to immense suffering for the patients. One way to facilitate the healing of these wounds is through autologous adipose tissue transplants. However, the implanted tissue needs to be vascularized or it will suffer from necrosis. To combat this Stromal vascular fraction (SVF), which is isolated from fat, can be utilized as it has been shown to promote both vascularization and the wound healing process. In this project, we evaluate a method that combines SVF with 3D Bioprinting to create thick fat grafts for in situ vascularization.
Adipose tissue was taken with consent from patients undergoing plastic surgery and was isolated with MiniStem, the device from JoinTechLabs, USA. Two MiniStem protocols were run: (i) lipoaspirate was fractured toward macerated fat graft and (ii) lipoaspirate was enzymatically treated in order for SVF harvest. Collected SVF was analyzed with FACS. Both fractions were mixed with a hydrogel composed of a mix of nanocellulose and alginate. The resulting cell-laden hydrogels (bioinks) were 3D Bioprinted as gridded constructs with CELLINKs INKREDIBLE+ bioprinter. The properties of the final constructs and bioinks were evaluated from a rheological perspective using a rheometer and O-prints, a method developed in-house.
The o-print showed that the mixed hydrogels were homogenous and easily printable. Rheology testing revealed that the crosslinked bioink also displayed properties like that of the extracellular matrix. FACS of the extracted SVF fractions showed the presence of a heterogeneous cell population with a substantial presence of ASCs, pericytes, and endothelial progenitors.
FACS data for SVF isolated with Ministem
DISCUSSION & CONCLUSIONS:
We have shown that we can isolate both fat and SVF from the same liposuction procedure. These results also show that fat and SVF isolated with the MiniStem and mixed with biopolymers contain relevant cells and possess good printability. High expression of angiogenic markers in both protocols strongly indicates potential angiogenic capacity.
Nanofibrillar Scaffold with Plated Adipose-Derived Stem Cells, Its Use for Lymphedema Treatment in Rats, and Path for Clinical Application
Gloria Sue, Dung Nguyen, Dimitris Dionysiou, Tatiana Zaitseva, Cristhian Montenegro, Peter Tabada, Peter Deptula, Derrick Wan, Nathan Katz, Michael Paukshto, Stanley Rockson.
Stanford University, Stanford, CA, US
Aristotle University of Thessaloniki, Greece
Fibralign Corp, Union City, CA, US
Jointechlabs, San Francisco, CA, US
To address the current deficit of sustainable lymphedema treatment, we investigated lymphatic regeneration guided by thread-like aligned nanofibrillar collagen scaffolds (BioBridge), which facilitate cell attachment, alignment, and migration. In this study, we tested our hypothesis that implantation of BioBridge with seeded Adipose-Derived Stem Cells (ADSCs) can reduce lymphedema when used in animals with developed lymphedema.
The rat lymphedema model involved inguinal and popliteal lymphadenectomy followed by irradiation. Subjects that developed lymphedema one month after lymphadenectomy/irradiation either received implantation of BioBridge with allogeneic ADSCs (treatment group) or remain untreated (control group). All subjects were observed for 4 months after lymphadenectomy. The change in affected to unaffected limb volume ratio was evaluated using CT-based volumetric analysis. Lymph flow and lymphangiogenesis were also assessed by ICG.
Subjects in the treatment group showed a reduction in affected limb volume (affected/non-affected limb volume ratio decreased from 113% to 97% (p <0.02)). ICG fluoroscopy demonstrated lymph flow and formation of lymphatics towards the contralateral groin in the direction of the implanted scaffolds. Conducted immunogistohistology supported the findings.
These data show that in the rat lymphedema model, the treatment of established lymphedema with BioBridge and ADSC substantially reduces lymphedema.
In preparation for a clinical application, we characterized human ADSC plated on BioBridge by FACS and compared manual ADSC isolation protocol with isolation using MiniStem system which is suitable for use in a clinical setting.
Combining Freshly Isolated Adipose-derived Cells With Regenogel-OSP
Nathan Katz, MSc, Ph.D., Jointechlabs, Inc., USA Avner Yayun, MD, Ph.D., Procore Biomed, Israel
Procore Biomed has developed a hyaluronic-acid – plasma cross-linked hydrogel “RegenoGel” suitable for the growth and differentiation of skeletal tissue stem and progenitor cells.
Jointechlabs has provided adipose-derived cell fraction obtained by the “Mini-Stem System”, which contains a range of 2-8% of mesenchymal stem cells with a potential chondroprotective effect on the joints in patients suffering from Knee OA.
Procore tested several parameters for the growth and differentiation of these cells when embedded in Regenogel OSP-based hydrogels. The hydrogels were prepared using the patient’s own autologous plasma linked to Regenogel-OSP-activated HA. Approximately 1 million cells (corresponding to approximately 40-50,000 MSCs) were mixed with the conjugate in loose-cap 5 ml falcon tubes and embedded within the hydrogel by the addition of Thrombin (approximately 0.25 IU/gel). 2 hrs later growth medium (1 ml; DMEM: F12) was added on top of the hydrogel and the tubes were placed in a 5% CO2 Incubator for different time points.
The integrity of the hydrogel was monitored by visual inspection of the intact hydrogel over time. Survival and proliferation of the cells were monitored using the metabolic dye Alamar blue. Cell differentiation was monitored using a functional ELISA for the presence of VEGF in the culture medium. Chondrogenic differentiation was monitored by measuring soluble glucosaminoglycans (sGAG). The effect of the proliferation and differentiation of these cells within the hydrogel was monitored with or without the addition of 10ng/ml of FGF2 twice weekly as a positive control for MSCs survival and proliferation.
The differentiation and proliferation of ADCs in Procore’s Regenogel-OSP. A. Proliferation is delayed without FGF2 but reaches similar levels after approximately two weeks. B. VEGF signal begins to rise after approximately one week in culture in the presence of FGF2, and after 12 days in the absence of FGF2, reaching similar levels at 15 days in culture. C. Soluble Glucosaminoglycans (sGAG) increase parallels VEGF and Alamar Blue signal increase.
Hydrogel integrity: All hydrogels remained fully intact after 15 days in culture, and displayed no signs of degradation.
Cell survival and proliferation: There was excellent survival and proliferation of the cells both with and without FGF2. FGF2 moderately accelerated the proliferation at initial time points (approximately one week in culture).
Secretion of VEGF: VEGF as a major angiogenic stimulator is largely secreted by mesenchymal stem cells (MSCs), and serves as a marker for MSC potency. A sharp increase in VEGF levels produced by the embedded cells indicates good survival and retention of active MSCs within the hydrogel for at least 15 days.
Chondrogenic differentiation: soluble glucosaminoglycans are secreted into the medium by differentiating chondrogenic cells. Indeed, a sharp rise beginning after one week in culture was detected.
We continue to follow up on the integrity, survival, and differentiation of MSCs in the Hydrogel over time.
Short Review: Non-cultured Adipose-derived MSCs for Treatment of OA, Jointechlabs, Inc.
Treating patients with OA presents a significant challenge for physicians as no therapies to date have demonstrated efficacy in curing or even halting disease progression. Therefore, most approaches initially target pain management and factors that may be exacerbating stress on the joint.
MSCs could provide an ideal source for direct regeneration of joint surfaces. While stem cells can both differentiate into new cartilage cells as well as suppress inflammation, recent studies have found that stem cells can also combat OA through paracrine mechanisms. They release important cytokines such as epidermal growth factor (EGF), transforming growth factor beta (TGFB), vascular endothelial growth factor (VEGF), as well as other cytokines and new cartilage proteins that are essential in combating OA and degenerative processes. It has also been suggested that stem cells could release cytokines and proteins that could help combat neurogenic pain, which would have numerous benefits in treating OA pain : – https://www.ncbi.nlm.nih.gov/pubmed/23881068 ; – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880954/ ; – https://www.ncbi.nlm.nih.gov/pubmed/25512139 .
Regeneration of joint tissues has been documented after injection of MSCs; however, some studies have found that reconstitution of tissue is primarily from native cells and relatively few transplanted cells : https://www.ncbi.nlm.nih.gov/pubmed/14673997
Other studies have shown that the cell signaling milieu is altered after the administration of MSCs with a subsequent increase in Type II collagen production by the host (https://www.ncbi.nlm.nih.gov/pubmed/22750747). Together, these factors suggest that MSCs may be orchestrating the reparative response rather than directly replacing damaged areas. This is in line with the well-documented anti-inflammatory and immunomodulatory role of MSCs (https://www.ncbi.nlm.nih.gov/pubmed/25426250). One of the breakthrough studies recently published has clearly demonstrated the attachment of MSCs to the full-thickness cartilage defects in rat models. Furthermore, these cells were found in abundance in the defect area 28 days after injection. What is intriguing is that the cells did not participate directly in the regeneration of the host cartilage in the long run since no tracking markers were observed 6 months following the injection. The study concluded that MSCs did not give rise to new chondrocytes for long-term regeneration and the paracrine effect played a major role in the recruitment of the host regenerative capabilities (https://insight.jci.org/articles/view/87322).
Adipose stem cells/adipose-derived stromal cells (ASCs) have gained attention due to their abundance, excellent proliferative potential, and minimal morbidity during harvest. Adipose-derived mesenchymal stem cells (ADSCs) can be harvested from the patient’s own adipose tissue via surgical liposuction. These advantages lower the cost of cell therapy by alleviating the time-consuming procedure of culture expansion : https://www.ncbi.nlm.nih.gov/pubmed/?term=Fulzele%20S%5BAuthor%5D&cauthor=true&cauthor_uid=27510262
ADSC therapy for OA in animal studies is well documented (https://www.ncbi.nlm.nih.gov/pubmed/26987846). Toghraie et al. demonstrated that ADSCs derived from IFPs in rabbits given to rabbits with OA-induced knees had less cartilage destruction, less subchondral sclerosis, less osteophyte buildup, as well as better cartilage overall than the control group (https://www.ncbi.nlm.nih.gov/pubmed/20591677). It also was demonstrated that autologous ADSC therapy decreased the progression of degeneration in cartilage and in the synovial membrane, improving meniscal repair. The regenerative effect of autologous ADSCs is dose and time-dependent (https://www.ncbi.nlm.nih.gov/pubmed/23360790). Another group also reported cartilage regeneration following autologous ADSC therapy in a surgically induced osteoarthritic sheep model. Autologous ADSCs were labeled and intra-articularly injected, leading to the cells populating the area of damaged cartilage as well as a decreased progression of OA : https://www.ncbi.nlm.nih.gov/pubmed/24911365
Several clinical studies also prove ADSCs’ efficacy in treating OA in human patients. Koh et al. treated patients with knee OA undergoing arthroscopic debridement with injected autologous ADSCs derived from IFPs and prepared in platelet-rich plasma (PRP). Treated patients demonstrated improved mobility and function in the affected knees, reduced pain levels, and better clinical prognoses in a 1-year follow-up: https://www.ncbi.nlm.nih.gov/pubmed/22583627
Some authors found the patients had significantly improved Western Ontario and McMaster Universities Osteoarthritis (WOMAC) pain scores, VAS pain scores, and cartilage regeneration as confirmed by MRI following 2 years of follow-up: https://www.ncbi.nlm.nih.gov/pubmed/23375182
In a different proof-of-concept clinical trial, autologous ADSCs were injected in patients with knee OA. The high-dose injection group had increased WOMAC scores 6 months after injections, decreased cartilage defects in affected areas, and increased cartilage volumes with thick, hyaline cartilage-like regeneration (https://www.ncbi.nlm.nih.gov/pubmed/24449146).
In 2011, Pak demonstrated the potential of ADSCs in osteonecrosis of the hip and OA in the knees of several patients. Results revealed bone formation in the osteonecrosis patients as well as cartilage regeneration in the OA knee patients. These patients’ MRIs had increased meniscus cartilage volume and thickness due to the ADSCs injections (https://www.ncbi.nlm.nih.gov/pubmed/21736710).
These results further proved the promising efficacy of autologous ADSCs in treating OA in humans, as well as demonstrated its safety as there were no adverse events. More similar clinical trials are necessary to further prove ADSCs’ efficacy for routine use in the human OA setting and more precisely define the mechanism of action. Last, but not least, it has been very recently documented that stem cells help dying or damaged cells by “recharging their mitochondrial batteries” in different organs, including joints: – https://www.ncbi.nlm.nih.gov/pubmed/24431222; – https://peerj.com/articles/3468/ .
In a degenerative joint, the mitochondria have been extensively exhausted and this reduces the functionality of cells. Healthy stem cells that have been injected into the affected joint, can rejuvenate damaged cells by transferring their “fully charged” mitochondrial batteries into the damaged cells. This final step completes a cascade of events that take place in the osteoarthritic joint (http://docplayer.net/21035327-Role-of-mitochondria-in-mesenchymal-stem-cells.html). The inactivation of the macrophages and the secretion of “helper” growth factors explain the long-term anti-inflammatory effect seen particularly with a stromal vascular fraction (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3296619/). This mechanism of action shows how stem cells may decrease pain and swelling. The above model also suggests that stem cells have a disease-modifying effect, by restoring the balance of cells within the joint: there is an increase in the number of “facilitating” stem cells and a decrease in the number of “destructive” macrophages, reducing this way the self-destruction of the joint.