Page 373 - Advances in Biomechanics and Tissue Regeneration

370 18. CARTILAGE REGENERATION AND TISSUE ENGINEERING

Another important question is the chondrocyte density required to regenerate articular cartilage. Human chondro-
cytes exhibit a poor proliferation rate, which often limits their use in cartilage regeneration. Finally, Roberts et al. [9]
observed no reduction in terms of clinical benefit from autologous chondrocyte implantation (ACI), which related to
the age of the patient. For these reasons, other cells exhibiting chondrogenic potential but higher proliferation rates are
required.

18.4.1.2 Mesenchymal Stem Cells
Mesenchymal stem cells (MSCs) are a valuable cell source and a useful alternative for cartilage engineering because
of their chondrogenic potential and the fact that they can be isolated from various tissues (Fig. 18.6), as described later.

18.4.1.2.1 BONE MARROW
Bone marrow (BM) is one of the best-known sources of MSCs that have been widely used for cartilage regeneration
either alone or seeded onto scaffolds facilitating implantation into defects. Both approaches have been successful in the
laboratory and the clinic; hyaline cartilage-like tissue part-filled defects and were associated with improvements in the
quality of life and joint function [60]. BM-MSCs are used when the microfracture technique is applied; the cells flow
toward the defect site and then differentiate into chondrocytes if the microenvironment and mechanical stimulation
are appropriate, as we showed in an in vivo animal model [64, 65].
However, some studies found no remarkable benefits when using BM-MSCs to repair cartilage defects; the new
cartilage was fibrocartilaginous in nature or even calcified. Also, the proportion of MSCs in BM is low (0.01%–
0.001%), and their differentiation potential falls with increased expansion in vitro. Finally, morbidity associated with
cell harvesting points to the need for other MSC sources [60].

18.4.1.2.2 ADIPOSE TISSUE
Adipose stromal/stem cells (ADSCs) can differentiate into chondrocytes, adipocytes, or osteoblasts, among other
cell types [66]. ADSCs are readily accessible as they can be isolated from adipose tissue routinely available after lipo-
suction surgery and expand quickly in vitro [67, 68]. Another advantage of such MSCs is yield; the number of MSCs
obtained from 100g of adipose tissue is 300-fold that from 100mL of BM. Several in vitro studies have found
that ADSCs exhibit chondrogenic differentiation when first cultured under appropriate 2-D conditions and then in

FIG. 18.6 Sources of mesenchymal stem cells. Diverse sources are used to differentiate cells into chondrocytes.

II. MECHANOBIOLOGY AND TISSUE REGENERATION