Scope of tissue engineering - Biomedical Engineering Desk Reference - page 707

Table 7.2-9 Commonly used markers for stem cells and differentiated cell types

Tissue Marker Cell type Significance

CD34 þ Scal þ Lin profile Bone marrow Mesenchymal stem cell Into adipocyte, osteocyte, chondrocyte,

and myocyte

CD29, CD44, CD105 Mesenchyme A type of cell adhesion molecule

Bone RunX Transcriptional activatori

ALP Preosteoblast, osteoblast Before the expression of OCN

OCN Osteoblast Before and during matrix mineralization

Cartilage Type II and IV collagen Chondrocyte Synthesized specifically by chondrocyte

Sulfated proteoglycan Chondrocyte Synthesized by chondrocyte

Fat ALBP Adipocyte Adipocyte lipid-binding protein

Nervous system Nestin Neural progenitor A marker of neural precursors

b -Tubulin-III Neuron Indicative of neuronal differentiation

Muscle MyoD and Pax7 Myoblast, myocyte Secondary transcriptional factors

Myosin heavy chain Cardiomyocyte A component of contractile protein

Myosin and MR4 Skeletal myocyte Secondary transcriptional factors

Blood vessel CD34 Endothelial progenitor Cell surface protein

Flkl Endothelial progenitor, endothelial cell Cell surface receptor protein

VE-cadherin Smooth muscle cell Cell adhesion molecule

some almost differentiated cells have widely been used in
clinical tissue engineering. Among them are notably fi-
broblasts, keratinocytes, osteoblasts, endothelial cells,
chondrocytes, preadipocytes, adipocytes, and tenocytes.
In the following, we will focus on chondrocytes as rep-
resentative of differentiated cells.
Despite a large number of studies achieved using
chondrocytes, isolation of autologous chondrocytes for
human use is invasive, requiring a biopsy from a non-
weight-bearing surface of a joint or a painful rib biopsy. In
addition, the ex vivo expansion of a clinically required
a number of chondrocytes from a small biopsy specimen,
which may itself be diseased, is hindered by deleterious
phenotypic changes in the chondrocyte. Bone marrow-
derived MSCs have been reported to differentiate into
multiple cell types of mesenchymal origin. Bone
marrow is a reservoir of both hematopoietic and non-
hematopoietic stem cells. The MSCs produce tissues
such as cartilage, bone, fat, and tendon. These tissues
are used daily by plastic and orthopedic surgeons for the
repair and augmentation of tissue defects. For these
tissues or organ repair or replacement, tissue engineers
seek to manipulate cell biology and cellular environ-
ments. However, to date, few tissue-engineered sys-
tems provide an autologous, minimally invasive, and
easily customizable solution for the repair or augmen-
tation of cartilage defects using MSCs.
The activity and function of articular chondrocytes
during skeletal growth differ from those found after
completion of growth. Chondrogenesis begins in the
central core of the developing limb end. First, cartilage is

formed from undifferentiated mesenchymal cells that
cluster together and synthesize cartilage collagen, pro-
teoglycans, and noncollagenous proteins. Type II collagen
forms the primary component of the cross-banded col-
lagen fibrils. The organization of these fibrils, into a tight
meshwork that extends throughout the tissue, provides
the tensile stiffness and strength of articular cartilage,
and contributes to the cohesiveness of the tissue by
mechanically entrapping the large proteoglycans. The
tissue becomes recognizable as cartilage under light mi-
croscopy, when an accumulation of matrix separates the
cells and they assume spherical shape. In growing in-
dividuals, the chondrocytes produce new tissue to
expand and remodel the articular surface. With skeletal
maturation, the rates of cell metabolic activity, matrix
synthesis, and cell division decline. After completion of
skeletal growth, most chondrocytes probably never
divide, but rather continue to synthesize collagens, pro-
teoglycans, and noncollagenous proteins. This continued
synthetic activity suggests that the maintenance of ar-
ticular cartilage requires substantial ongoing remodeling
of the macromolecular framework of the matrix, and the
replacement of degraded matrix macromolecules. With
aging, the capacity of the cells to synthesize some types
of proteoglycans and their response to stimuli, including
growth factors, decrease. These age-related changes may
limit the ability of the cells to maintain the tissue, and
thereby contribute to the development of degeneration
of the articular cartilage.
To promote restoration of normal biomechanical
function and long-term integrity of the articular cartilage,