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Aziz, E. Fat Pad-Derived Mesenchymal Stem Cells. Encyclopedia. Available online: https://encyclopedia.pub/entry/14779 (accessed on 20 June 2024).
Aziz E. Fat Pad-Derived Mesenchymal Stem Cells. Encyclopedia. Available at: https://encyclopedia.pub/entry/14779. Accessed June 20, 2024.
Aziz, Eftekhari. "Fat Pad-Derived Mesenchymal Stem Cells" Encyclopedia, https://encyclopedia.pub/entry/14779 (accessed June 20, 2024).
Aziz, E. (2021, September 30). Fat Pad-Derived Mesenchymal Stem Cells. In Encyclopedia. https://encyclopedia.pub/entry/14779
Aziz, Eftekhari. "Fat Pad-Derived Mesenchymal Stem Cells." Encyclopedia. Web. 30 September, 2021.
Fat Pad-Derived Mesenchymal Stem Cells
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Cartilage is frequently damaged with a limited capacity for repair. Current treatment strategies are insufficient as they form fibrocartilage as opposed to hyaline cartilage, and do not prevent the progression of degenerative changes. There is increasing interest in the use of autologous mesenchymal stem cells (MSC) for tissue regeneration. MSCs that are used to treat articular cartilage defects must not only present a robust cartilaginous production capacity, but they also must not cause morbidity at the harvest site. In addition, they should be easy to isolate from the tissue and expand in culture without terminal differentiation. The source of MSCs is one of the most important factors that may affect treatment. The infrapatellar fat pad (IPFP) acts as an important reservoir for MSC and is located in the anterior compartment of the knee joint in the extra-synovial area. 

 

infrapatellar fat pad Cartilage mesenchymal stem cells adipose tissue osteoarthritis Tissue engineering Stem Cells Regenerative Medicine

1. Introduction

1.1. Articular Cartilage

Articular cartilage is a specialized connective tissue that lacks blood vessels, nerves, and lymphatic tissue. Consequently, cartilage tissue has limited capacity for repair and the progression of focal cartilage defects leads to more generalized degenerative changes or osteoarthritis [1]. Articular cartilage damage is a disabling disease characterized by fibrillation and subsequent destruction of the articular cartilage surface, frequently including subchondral bone damage inducing more generalized changes [2]. The adjoining synovium in articular cartilage disease includes biomarkers for significant inflammation, including Substance P, which further stimulates a local inflammatory response [3][4]. Consequently, oedema and inflammation of the infrapatellar fat pad (IPFP) and the synovial membrane cause the progression of osteoarthritis as well as articular cartilage loss that often necessitates full joint replacement. Furthermore, the synovial membrane and IPFP may interact with each other, affecting the development and progression of osteoarthritis [4][5].

1.2. Past and Current Articular Cartilage Treatments

Cartilage defects cause a significant disease burden and a previous study indicated that more than of 60% of knees undergoing arthroscopy have articular defects [6]. If these defects are left untreated, or managed suboptimally, they lead to the progression of more widespread degenerative changes. There are several methods for treating articular cartilage defects depending on the anatomical location, extent, shape, and depth of the cartilage defect, and age of the patient [7] (Table 1). The operative treatment techniques mentioned in Table 1 result in the formation of the less desirable fibrocartilage, or hyaline-like cartilage, as opposed to hyaline cartilage. Fibrocartilage has suboptimal biomechanical properties and does not prevent the progression of the degenerative changes of osteoarthritis [8]. Studies on cell-based techniques, including Autologous Chondrocyte Implantation (ACI) and Matrix-Assisted ACI (MACI), have highlighted the disadvantages of using fully differentiated chondrocytes, such as their difficulty in extraction, isolation, expansion, and growth in vivo after implantation. It is of the highest importance to find alternative cell sources.
Table 1. Non-operative and operative treatment techniques for articular cartilage defects.
Technique Effect Reference
Non-operative Methods Pharmacotherapy drugs (steroidal and non-steroid anti-inflammatory drugs, glucosamine, chondroitin sulphates, etc.) to control symptoms [9]
Abrasion Arthroplasty Creation of a rough surface in the damaged area in order to form fibrocartilage (subchondral bone is not directly accessed) [10]
Arthroscopic Debridement Removal of the damaged part of the tissue, allowing the subchondral bone to initiate the healing process [11]
Autologous Chondrocyte Implantation (ACI) Transplantation of isolated and expanded chondrocytes from healthy cartilage to the defected area [12]
Chondroplasty Utilizes laser or radiofrequency-based probes to smooth the damaged edges of cartilage [13]
Matrix-assisted ACI (MACI) Isolated and expanded autologous chondrocytes are combined with a scaffold which is implanted into the defect site [14]
Microfracture (subchondral drilling) Subchondral bone is stimulated by drilling, allowing the bone marrow MSCs to migrate to the damaged area and form fibrocartilage [15]
Mosaicplasty Osteochondral autografts or allografts are transferred from a donor site to the defect site [16]

1.3. Cell-Based Therapies

Recent advances in developing therapeutic strategies for treating articular cartilage defects [17][18] have focused on stem cell therapies and tissue regeneration to prevent the progression to osteoarthritis [19]. Stem cells have shown superiority in treating articular cartilage defects due to their ease of isolation, expansion, and culture in preliminary studies, and are a promising method for promoting articular cartilage regeneration [20]. Mesenchymal stem cells (MSCs), in contrast to autologous chondrocytes, possess a greater capacity to expand in vitro [19]. The use of MSCs does not raise ethical concerns, as is the case with embryonic stem cells. Many questions need to be answered before stem cells are routinely used for cartilage defects, including the optimal stem cell source, an optimal extraction, isolation, and expansion protocol, the need for scaffolds, and cost. Although adipose tissue-derived MSCs have a lower chondrogenic capacity in comparison with bone marrow mesenchymal stem cells [21], they can be harvested in a less invasive and cost-effective manner with liposuction. Due to this easier access, the therapeutic application of adipose tissue-derived MSCs is increasing [22]. For all of the above reasons, the IPFP has become an area of high interest in regenerative medicine since it stores MSC.
Despite the promise of the IPFP as a source of MSC for regenerating articular cartilage, very few reviews exist on this subject. In this review, for the first time, the authors detail several IPFP cell-based therapies, their current progress towards healing articular cartilage damage, and the most recent advances in the use of IPFP-derived MSCs for cartilage repair.

2. Advantages of Adipose Tissue-Derived MSCs for Articular Cartilage Repair

The presence of MSCs in adipose tissue from liposuction was first reported in 2001 by Zuck et al. [23]. Adipose tissue-derived MSCs have also demonstrated a greater ability to differentiate into other lineages in pre-clinical studies compared to umbilical cord stem cells [2][24]. Adipose tissue is one of the most easily accessible tissues for the extraction of MSCs and is often discarded after liposuction. Since increased BMI and adipose tissue content are related to articular cartilage damage, removal of adipose tissue through liposuction and subsequent isolation of adipose tissue-derived MSCs can be well suited for treating articular cartilage damage [25][26].
Due to the potentially wide applications of MSCs in regenerative medicine, it is essential to have access to a reliable and reproducible MSC source. Adipose tissue-derived MSCs are feasible and promising candidates for cell-based therapies [27], and they can be differentiated into adipose tissue, bone, cartilage, and muscle [28][29]. Studies have confirmed chondrogenic differentiation of human adipose tissue-derived MSC pellet cultures by the expression of target tissue markers [30]. After harvesting of adipose tissue using liposuction aspiration or needle biopsy, adipose tissue-derived MSCs were isolated from adipose tissue. The tissue was washed with phosphate-buffered saline and a penicillin/streptomycin solution before being minced. To further dissolve any adipose tissue clumps or aggregates, the adipose tissue was pipetted up and down numerous times to facilitate mechanical disruption of the extracellular matrix. The tissue was then placed in a plate of sterile tissue culture dishes and 0.05% of a collagenase digestion buffer for tissue digestion after the debris was removed. The supernatant was aspirated after collagenase inactivation with K-NAC medium supplemented and 10% fetal calf serum (FCS), and the cell pellet was resuspended in a K-NAC medium supplemented with 10% FCS. Following centrifugation, the cell suspension was blended and filtered using a 100-μm cell strainer. Lastly, cell pellets were plated onto a tissue culture plate and cultured in an incubator at 37 °C with 5% CO2 [22]. Such processes are now commonly used for ADSC isolation and can be used for articular cartilage repair.
Over the last two decades, stem cell-based therapies using adipose tissue-derived MSCs have been expanding, as supported by their strong therapeutic potential. Studies have reported that the effect of stem cells derived from different tissues differ according to the site of extraction [31]. Adipose tissue is easier to access than other tissues and obtaining MSCs from this tissue is less invasive [32]. Compared to bone marrow, the process of harvesting tissue from adipose tissue is less invasive, and studies suggest a greater cell yield per unit of tissue as well [33]. Studies suggest that adipose tissue-derived MSCs have a smaller cell body than bone marrow-derived MSCs and have different gene expression and cell surface receptors. Commonly used markers include CD90, CD44, CD29, CD105, CD13, CD34, CD73, CD166, CD10, CD49e, and CD59, which are all positive, while CD31, CD45, CD14, CD11b, CD19, CD56, and CD146 are all negative in adipose tissue-derived MSCs. In addition, the positive expression of HLA-ABC and STRO-1 as well as the negative expression of HLA-DR are also features of adipose tissue-derived MSCs [34]. ADSCs can all be passaged in vitro up to passage 10 with no karyotype abnormalities detected [35]. Unlike bone marrow-derived MSCs, the number, viability, and proliferation capacity of ADSCs do not appear to be related to patient age.
Despite the important advantage of adipose tissue-derived MSCs in that they are easier to harvest and isolate, and their increased ability to proliferate and differentiate into chondrocytes, an incomplete understanding of the processes and mechanisms of their differentiation have limited their clinical applications [24]. Studies have reported important differences between various MSC sources, and this has implications on the choice of cells for articular cartilage regeneration [36][37]. MSCs from various tissues vary in their proliferation and differentiation properties (Table 2). An important challenge with adipose tissue-derived MSCs is the creation of fibrous and hypertrophic cartilage instead of articular hyaline cartilage [36].
Table 2. A summary of MSC properties with respect to their isolation, proliferation, and differentiation [37][38].
  Adipose Tissue-Derived MSCs Bone Marrow-Derived MSCs Umbilical Cord-Derived MSCs
Ease of Harvest and Isolation +++ + ++
Amounts of Tissue Obtained +++ ++ +
Capacity for Proliferation and Colony Formation ++ + +++
Maintenance of Function Irrespective of Donor Age ++ + +++
Suitability for Soft Tissue Regeneration (e.g., skin, cartilage, etc.) +++ ++ +
Suitability for Hard Tissue Re-generation (e.g., bone, tooth, etc.) + ++ +++
+ weak, ++ moderate, +++ strong.

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