Steven Nicoll, Ph.D.
nicoll@seas.upenn.edu
Assistant Professor
of Bioengineering
Assistant
Professor of Orthopaedic Surgery
Member,
Institute for Medicine and Engineering
Ph.D. Bioengineering,
2000, University of California, Berkeley and San Francisco
B.S.E. Bioengineering,
1994, University of Pennsylvania
Research Interests
AREAS
OF EXPERTISE
Connective
tissue engineering, biomaterials, cartilage cell biology
AREAS
OF SPECIAL INTEREST
Epigenetic
Control of Cellular Phenotype. Recent advances in tissue engineering
have increased the need for specialized cell populations to promote
tissue regeneration. Embryonic stem cells have been investigated
for such applications and hold great therapeutic promise. However,
practical and ethical considerations may ultimately limit the widespread
use of such progenitor cells. Our approach involves the conversion
of human dermal fibroblasts to specialized cell types by regulating
environmental cues such as oxidative and mechanical stresses that
govern cell differentiation. Thus far, we have successfully induced
dermal fibroblasts to differentiate into chondrocytes (i.e., cartilage
cells) and are currently using these cells to engineer articular
cartilage. We plan to extend these studies to explore whether such
fibroblasts may give rise to other cell types (i.e., bone and muscle-forming
cells) by modulation of similar epigenetic pathways.
Biomimetic
Scaffolds for Connective Tissue Repair. The success of implantable
materials depends heavily upon their ability to integrate with surrounding
host tissue. The incorporation of growth factors into carrier materials
as well as the immobilization of bioactive peptides which mimic
the cell binding domains of extracellular matrix macromolecules
are current approaches that we use to promote cell adhesion and
improve implant fixation and stability. A particular class of collagen
mimetic peptides has been shown to stimulate cell attachment and
differentiation on clinically relevant biomaterials. The interaction
of these collagen-like peptides with cell surface receptors and
their potential to generate precise, three-dimensional cellular
architectures are being characterized on materials used in the development
of living tissue surrogates.
Transcriptional
and Genetic Determinants of Chondrogenesis. We utilize an in vitro
model system for cartilage differentiation developed in our laboratory
to explore signal transduction pathways and identify novel genes
involved in chondrogenesis. Expanding on previous work with the
transforming growth factor-ß (TGF-ß) family of polypeptide
cytokines, we study the role of transcription factors that act downstream
of pathways mediated by TGF-ß family members. In addition,
we are attempting to isolate regulatory genes essential to cartilage
formation using a variety of techniques including differential display
reverse-transcription-PCR and gene microarray analyses. Cloning
of such genes may result in the discovery of novel growth and morphogenetic
factors that may be of use in clinical orthopaedics.
RECENT
PUBLICATIONS
1. Denker,
A. E., Nicoll, S. B. and Tuan, R. S. Formation of cartilage-like
spheroids by micromass cultures of murine C3H10T1/2 cells upon treatment
with transforming growth factor-ß1. Differentiation, 59:25-34,
1995.
2. Nicoll,
S. B., Denker, A. E. and Tuan, R. S. In vitro characterization of
transforming growth factor-ß1-loaded composites of biodegradable
polymer and mesenchymal cells. Cells Mater, 5:231-244, 1995.
3. Nicoll,
S. B., Radin, S., Santos, E. M., Tuan, R. S. and Ducheyne, P. In
vitro release kinetics of biologically active transforming growth
factor beta-1 from a novel porous glass carrier. Biomater, 18:853-859,
1997.
4. Denker,
A. E., Haas, A. R., Nicoll, S. B. and Tuan, R. S. Chondrogenic differentiation
of murine C3H10T1/2 multipotential mesenchymal cells I: Stimulation
by BMP-2 in high density micromass cultures. Differentiation, 64:67-76,
1997.
5. Nicoll,
S. B., Wedrychowska, A., Smith, N. and Bhatnagar, R. S. A new approach
to cartilage tissue engineering using human dermal fibroblasts seeded
on three-dimensional polymer scaffolds. Proc Mater Res Soc, 530:
3-6, 1998.
6. Nicoll,
S. B., Denker, A. E. and Tuan, R. S. Mesenchymal cell-based repair
of connective tissue defects: Application of transforming growth
factor-ß superfamily members and biodegradable polymer scaffolds.
Cells Mater, 9:99-122, 1999.
7. Nicoll,
S. B., Liang, C.-W. and Bhatnagar, R. S. Osteoblast-like cells exhibit
increased cellular attachment and expression of osteogenic markers
on e-PTFE membranes surface-modified with a collagen mimetic peptide.
Trans Soc for Biomater, 23:1161, 2000.
8. Nicoll,
S. B., Wedrychowska, A., Smith, N. R. and Bhatnagar, R. S. Modulation
of proteoglycan and collagen profiles in human dermal fibroblasts
by high density micromass culture and treatment with lactic acid
suggests change to a chondrogenic phenotype. Conn Tiss Res, 42:59-69,
2001.
9.Nicoll,
S. B., Barak, O., Csóka, A. B., Bhatnagar, R. S. and Stern,
R. Hyaluronidases and CD44 undergo differential modulation during
chondrogenesis. Biochem Biophys Res Comm, 292:819-825, 2002.
Bioengineering
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