Stem Cell, Bone Biology and Bone Tissue Engineering
In order to complement our work in cranial suture biology, distraction
osteogenesis, and calvarial re-ossification, the bone group also investigates
fundamental aspects of osteogenesis and bone formation with emphasis
on angiogenesis. The goal of this work is to understand how osteoblast
can form bone in very different environments (e.g. cranial suture, mandible,
or calvarial bone plates). For example, we have demonstrated that FGF-2
induces osteoblasts to produce VEGF (a potent angiogenic factor) as well
as BMP-2 (a potent osteogenic factor). In conjunction with our in vivo
model, we are learning that successful bone formation requires precise
regulation of angiogenesis and osteogenesis. Ultimately, we believe that
learning to manipulate osteoblast biology will lead to improve clinical
outcomes.
Stem Cell Biology and Therapies
Our group is interested in the biology of adipose tissue derived mesenchymal
stem cells (MSC) and their possible applications in tissue engineering.
Recently, colleagues at UCLA have demonstrated that mesenchymal stem
cells obtained from routine liposuction can differentiate into adipogenic,
osteogenic, chondrogenic, and myogenic cell types. Liposuction yields
large quantities of these MSCs making their potential use practical for
future clinical applications. We are beginning to explore the biology
of these adult-derived stem cells and their possible application to bone
healing, neural regeneration/repair, pancreas, muscle, cartilage and
liver replacement.
Selected Articles
Spector JA, Mehrara BJ, Luchs JS, Greenwald JA, Faganhol PS, Saadeh PB,
Steinbrech DS, Longaker MT: Expression of Adenovirally Delivered Gene
Products in Healing Osseous Tissues. Ann Plast Surg 44: 522-528, 2000.
Steinbrech DS, Mehrara BJ, Rowe NM, Dudziak ME, Luchs JS, Saadeh PB,
Gittes GK, Longaker MT: “Gene Expression of TGF-Beta,
TGF-Beta Receptor, and Extracelluar Matric Protein During Membraneous
Bone Healing in Rats. Plast Reconstr Surg 105: 2028-2038, 2000.
Steinbrech DS, Mehrara BJ, Saadeh PB, Greenwald JA, Spector JS, Gittes
GK, Longaker MT: Hypoxia Increases Insulin-like Growth Factor Gene Expression
in Rat Osteoblast. Ann Plast Surg 44: 529-534, 2000.
Saadeh PB, Mehrara BJ, Steinbrech DS, Spector JA, Greenwald JA, Chin
GS, Ueno H, Gittes GK, Longaker MT: Mechanisms of Fibroblast Growth Factor-2
Modulation of Vascular Endothelial Growth Factor Expression by Osteoblastic
Cells. Endocrinology 141: 2075-2083, 2000.
Steinbrech DS, Mehrara BJ, Saadeh PB, Greenwald JA, Spector JA, Gittes
GK, Longaker MT: VEGF Expression in an Osteoblast-like Cell Line is Regulated
by a Hypoxia Response Mechanism. Am J Physiology 278: 853-860, 2000.
Spector JA, Mehrara BJ, Greenwald JA, Saadeh PB, Steinbrech DS, Bouletreau
PJ, Smith LP, Longaker MT: Osteoblast Expression of Vascular Endothelial
Growth Factor is Modulated by the Extracellular Microenvironment. Am
J Physiology 280: C72-80, 2001.
Paccione MF, Warren SM, Spector JA, Greenwald JA, Longaker MT: A Mouse
Model of Mandibular Healing. J Craniofac Surg (Accepted for Publication).
Bouletreau PJ, Steinbrech DS, Spector JA, Warren SM, Greenwald JA, Mehrara
BJ, Detch RC, Longaker MT: Gene Expression of Transforming Growth Factor
Beta-3 and Tissue Inhibitor of Matalloproteinase-1 During Membranous
Bone Healing in Rats. J Craniofac Surg 11: 521-526, 2000.
Spector JA, Luchs JS, Mehrara BJ, Greenwald JA, Smith LP, Longaker MT:
Expression of Bone Morphogenetic Proteins during Memebranous Bone Healing.
Plast Reconstr Surg 107: 124-134, 2001
Fagenholz PJ, Warren SM, Greenwald JA, Bouletreau PJ, Spector JA, Crisera
FE, Longaker MT: Osteoblast Gene Regulation is Differentially Regulated
by TGF-B Isoforms. J Craniofac Surg 12: 183-190, 2001
Warren SM, Steinbrech DS, Mehrara BJ, Saadeh PB, Greenwald JA, Spector
JA, Bouletreau PJ, Longaker MT: Hypoxia regulates osteoblast gene expression.
J Surg Res 99: 147-155, 2001.
