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][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][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][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% CO
2 [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][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 [
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Suitability for Hard Tissue Re-generation (e.g., bone, tooth, etc.) |
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