Definition and principles of autologous regenerative therapy
Autologous Regenerative Therapy (ART) is described as an innovative medical discipline that aims to regenerate injured tissues or to stimulate their repair using the patient’s own biological resources. In this framework, ART applies the same natural principles as tissue engineering but is implemented through an easy, reproducible, and relatively fast procedure that can be performed in a single medical session. The technique utilizes the patient’s own cells, in particular autologous mesenchymal stromal/stem cells (MSCs), which are harvested and reintroduced into target tissues without extensive ex vivo manipulation.
A central principle of ART is the exploitation of the intrinsic reparative and trophic properties of MSCs derived from adipose tissue. Human adipose tissue has been identified as a source of multipotent mesenchymal stromal cells similar to those found in bone marrow, and these adipose-derived stromal/stem cells (ASCs or ADSCs) are localized within the stromal vascular fraction (SVF). The SVF contains interrelated cell populations, including ASC progenitors, pericytes, and endothelial progenitor cells, which together contribute to the regenerative potential of adipose tissue grafts.
In clinical ART protocols based on adipose tissue, donor fat is harvested with minimally invasive techniques, often using small cannulas and low negative pressure, and is processed with minimal manipulation such as washing and decantation rather than enzymatic digestion or high-speed centrifugation. This approach is intended to preserve cell viability and the structural integrity of micro-fragmented adipose clusters while maintaining a high content of viable stromal cells. Studies comparing guided harvesting with small side-port cannulas to standard liposuction with enzymatic digestion have shown that minimally manipulated micro-fragmented adipose tissue can yield a comparable amount of viable cells, supporting its use as a regenerative graft.
ART is typically performed as a single-step autologous procedure: adipose tissue is harvested, processed to obtain a micrograft enriched in SVF/ASCs, and then injected into the target site during the same session. In musculoskeletal applications, this may involve intra-articular injection of autologous micro-fragmented adipose tissue into osteoarthritic joints such as the knee or hip. The autologous nature of the graft is considered advantageous for tolerability, as the injected material is recognized as self and has been reported to be well tolerated, with postoperative courses characterized mainly by transient swelling and low-grade pain at the injection site.
Biological basis: stromal cells and tissue repair
The biological foundation of autologous adipose-based ART resides in the properties of adipose-derived stromal/stem cells (ASCs) and the broader SVF cell population. ASCs are plastic-adherent multipotent cells that can differentiate in vitro towards mesodermal lineages, including osteoblasts, adipocytes, and chondrocytes. They express mesenchymal markers such as CD73, CD90, and CD105 and lack hematopoietic markers including CD14, CD34, and CD45. This phenotype, combined with their multilineage differentiation capacity, underpins their potential role in the regeneration of cartilage, bone, and other mesenchymal tissues.
Beyond differentiation, ASCs and other stromal cells in the SVF exert important paracrine effects. They secrete bioactive molecules capable of stimulating angiogenesis and revascularization of fat grafts, and they display antifibrotic, anti-apoptotic, and immunomodulatory properties. These characteristics have been associated with clinical observations such as improved skin trophism, accelerated closure of complex wounds or ulcers, and enhancement of skin appearance after radiotherapy damage following adipose tissue grafting. The same paracrine mechanisms are considered relevant for musculoskeletal tissue repair, where modulation of inflammation, fibrosis, and vascularization can influence joint homeostasis and symptomatology.
Experimental work on adipose tissue harvested with SEFFI and micro-SEFFI systems has demonstrated that ASCs can be reliably isolated from micrografts obtained with small side-port cannulas. These cells show a good proliferation rate and retain the capacity to differentiate towards adipogenic, osteogenic, and chondrogenic lineages, confirming their stemness potential. Even when micro-SEFFI-derived tissue exhibits small cluster size and relatively low cellularity, stem cells can still be isolated, which partially explains the regenerative potential observed with autologous micro-SEFFI tissue grafts in clinical settings.
The SVF itself is a heterogeneous compartment composed of adipocyte progenitors, pericytes, endothelial progenitor cells, and transit-amplifying cells. This complex cellular milieu is thought to support tissue repair through coordinated actions on extracellular matrix remodeling, neovascularization, and local immune modulation. In the context of osteoarthritis and other degenerative conditions, adipose-derived MSCs have been reported to possess intrinsic capacity to contribute to the regeneration of cartilage, tendons, and bone, making them attractive candidates for orthopedic regenerative applications.
Clinical rationale and therapeutic goals
Osteoarthritis (OA) is characterized as a complex musculoskeletal disorder resulting from degeneration of articular cartilage, leading to joint pain, dysfunction, and progressive cartilage loss. Conventional conservative treatments, including physical therapy, lifestyle modification, pharmacologic agents, steroid injections, and intra-articular hyaluronic acid, are largely palliative and do not reverse or repair the degenerative nature of the disease. In this context, the clinical rationale for autologous regenerative therapy is to move beyond symptomatic relief and to harness the reparative capacity of adipose-derived cells to influence the underlying joint pathology.
ART based on intra-articular injection of autologous micro-fragmented adipose tissue aims to regenerate or stimulate repair of damaged joint tissues by delivering a concentrated source of SVF/ASCs, cytokines, growth factors, pre-adipocytes, and mature adipocytes directly into the osteoarthritic environment. ADSCs have been described as capable of differentiating into multiple cell types, including chondrocytes and endothelial cells, and of secreting bioactive molecules that promote angiogenesis and exert antifibrotic, antiapoptotic, and immunomodulatory effects. These combined actions provide a biological rationale for targeting both structural and inflammatory components of OA with a single autologous intervention.
Clinically, therapeutic goals of autologous adipose-based ART in OA include reduction of pain, improvement of joint range of motion, reduction of stiffness, and enhancement of overall function and quality of life. In a cohort of patients with hip and knee OA treated with intra-articular injection of autologous fat micrograft using a standardized device, improvements in range of motion of approximately 10 degrees were observed three months after treatment, accompanied by reductions in stiffness as reported by patients. Pain reduction, as measured by visual analogue scale (VAS), tended to emerge by three months and reached more pronounced levels at six months for the knee and between six and twelve months for the hip.
Another important clinical objective is to delay or potentially avoid major joint replacement surgery in selected patients. In the same series, a high proportion of patients reported satisfaction one year after treatment, with considerable improvement in pain and quality of life, and only a small subset proceeded to joint replacement over longer follow-up. The minimally invasive nature of the procedure, combined with the autologous origin of the graft and the generally favorable postoperative course at both donor and recipient sites, supports its consideration as a therapeutic option aimed at preserving joint function and postponing more invasive surgical interventions in appropriately selected cases.
Comparison with other regenerative approaches
Within the broader field of regenerative medicine, multiple cell-based strategies have been explored for musculoskeletal disorders, including the use of culture-expanded mesenchymal stem cells from various sources. In orthopedics, cartilage repair has been a pioneering area for the translational application of cell therapy, with stem cells used in conditions such as avascular bone necrosis, osteochondral defects, pseudoarthrosis, and traumatic cartilage lesions. Autologous adipose-based ART can be viewed as a specific implementation of these concepts, distinguished by its reliance on minimally manipulated micro-fragmented adipose tissue rather than extensively processed or culture-expanded cell products.
Adipose tissue has attracted substantial interest as an alternative stem cell source compared with bone marrow, due to its accessibility and high recovery of stromal cells. The identification of multipotent mesenchymal stromal/stem cells in human adipose tissue, with properties similar to bone marrow–derived MSCs, has led to the development of protocols that isolate SVF or culture-expanded ASCs for clinical use. Autologous micro-fragmented adipose tissue grafting represents a non-enzymatic, point-of-care approach that leverages the native SVF/ASC content without the need for enzymatic digestion or cell expansion, which may have regulatory and logistical implications distinct from other regenerative products.
From a technical standpoint, micro-fragmented adipose tissue harvested with small cannulas and minimal negative pressure has been shown to contain viable and proliferative cells in quantities comparable to tissue processed with enzymatic digestion. In a comparative study, adipose tissue obtained with 0.8 mm and 1 mm side-port cannulas yielded a similar amount of viable cells to liposuction tissue processed with collagenase, supporting the concept that minimally manipulated micrografts can serve as a practical alternative to enzymatically isolated SVF for regenerative applications. This contrasts with more complex automated or enzymatic systems designed specifically to isolate stromal cells, which may introduce additional variability and processing steps.
Clinical literature cited in the context of adipose-based ART includes studies on intra-articular injection of adipose-derived MSCs for knee osteoarthritis, as well as broader reviews on mesenchymal stem cells and osteoarthritis and on the safety of intra-articular cell therapy with culture-expanded stem cells. These works collectively frame autologous adipose micrografting as part of a continuum of MSC-based interventions, ranging from minimally manipulated tissue grafts to culture-expanded cell products. While specific comparative outcome data between these approaches are not detailed in the available documents, the emphasis on a single-session, minimally invasive, autologous procedure distinguishes micro-fragmented adipose tissue therapy from more complex cell manufacturing strategies.
Indications in musculoskeletal medicine
The primary musculoskeletal indication described for autologous adipose-based ART is osteoarthritis of weight-bearing joints, particularly the knee and hip. OA is characterized by degeneration of articular cartilage, joint pain, stiffness, and functional limitation, with risk factors including age, heredity, obesity, and biomechanical alterations such as joint malalignment or laxity. As the prevalence of OA is expected to rise with population aging and increasing obesity, there is a growing interest in regenerative strategies that may modify disease progression or improve symptoms beyond what is achievable with conventional conservative measures.
In a clinical series, patients with initial-stage degenerative OA of the hip and/or knee were treated with intra-articular injection of autologous micro-fragmented adipose tissue obtained using a standardized device. Inclusion criteria included men and women aged 20 to 80 years with symptomatic hip or knee OA confirmed and graded by radiography and magnetic resonance imaging. The majority of procedures involved the knee, with a smaller proportion targeting the hip, and radiographic grading systems such as Kellgren–Lawrence for the knee and Tönnis for the hip were used to characterize disease severity, with average grades in the mild to moderate range.
The procedure consisted of harvesting adipose tissue from a donor site, processing it through washing and decantation to obtain a micrograft enriched in SVF/ASCs, and injecting it intra-articularly under local anesthesia. The entire process could be completed in approximately 60 to 70 minutes. Postoperative management included compression at the donor site and temporary restriction of sports activities, while follow-up assessments at three, six, and twelve months focused on pain, range of motion, stiffness, and patient-reported outcomes. The donor site course was generally uneventful aside from minimal discomfort, edema, and ecchymosis, and the injected joints exhibited transient swelling and low-grade pain for several days without reported major complications.
Clinical observations suggested that better outcomes in terms of pain reduction and functional improvement were associated with younger age and lower OA grade at baseline, whereas older patients with more advanced OA showed less pronounced gains in mobility but still experienced reductions in pain. Improvements in range of motion and stiffness tended to appear within three months, while maximal pain reduction was typically observed around six months for the knee and between six and twelve months for the hip. These findings support the use of autologous adipose-based ART as a minimally invasive option in patients with early to moderate OA of the knee and hip, with the potential to improve symptoms and delay more invasive surgical interventions.
Supporting scientific evidence
The scientific basis for autologous adipose-based ART is supported by both preclinical and clinical evidence. Foundational work identified human adipose tissue as a source of multipotent mesenchymal stromal cells, demonstrating that adipose-derived cells share key properties with bone marrow–derived MSCs, including multilineage differentiation potential. Subsequent studies characterized the SVF as a heterogeneous cell population containing ASC progenitors, pericytes, and endothelial progenitor cells, and established the capacity of ASCs to differentiate into adipogenic, osteogenic, and chondrogenic lineages in vitro. These findings provide a mechanistic framework for the use of adipose-derived cells in tissue repair and regeneration.
Clinical and translational research has documented the regenerative potential of adipose-derived cells in various contexts. Reports include the use of autologous adipose SVF in the treatment of traumatic calvarial defects, as well as numerous clinical trials investigating ASCs in tissue reconstruction and regeneration across indications such as bone and cartilage diseases, autoimmune conditions, and nervous system disorders. In dermatologic and reconstructive applications, adipose tissue grafts enriched in SVF/ASCs have been associated with volumization and skin regeneration effects, improved skin trophism, and enhanced healing of complex wounds and radiotherapy-induced damage, supporting the broader concept of adipose-based regenerative therapy.
Specific to musculoskeletal medicine, reviews and clinical studies have examined the application of mesenchymal stem cells, including adipose-derived MSCs, in osteoarthritis. Cited works include analyses of the current state of OA treatment options using stem cells for regenerative therapy, research on the use of MSCs and their derived exosomes in OA, and clinical trials of intra-articular injection of autologous adipose tissue–derived MSCs for knee osteoarthritis. Additional publications have addressed the safety of intra-articular cell therapy with culture-expanded stem cells and have reported on adipose-derived stromal vascular fraction cell applications in OA patients. Collectively, these studies contribute to an evidence base that supports the feasibility and potential efficacy of MSC-based interventions in degenerative joint disease.
The clinical series on intra-articular injection of autologous micro-fragmented adipose tissue for hip and knee OA provides further practice-oriented evidence. In this cohort, a large majority of patients reported satisfaction one year after treatment, with considerable improvements in pain and quality of life. Only a small proportion proceeded to joint replacement over extended follow-up, and the procedure was associated with a favorable safety profile at both donor and recipient sites. While limitations such as the absence of a control group and the need for larger, controlled studies are acknowledged, these findings support the role of autologous adipose-based ART as a promising regenerative option in the management of osteoarthritis.
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