Lachlan J. Smith

About

Lachlan James Smith, Ph.D., is a Professor of Orthopaedic Surgery at the Perelman School of Medicine at the University of Pennsylvania, affiliated with the McKay Orthopaedic Research Laboratory. His research focuses on the pathophysiology and treatment of degenerative and developmental disorders affecting the spine and synovial joints. His work encompasses basic mechanistic studies, translational studies in animal models, and clinical studies in human patients, utilizing advanced techniques in molecular biology, biochemistry, and bioengineering. Dr. Smith's research bridges tissue engineering, biomaterials, drug delivery, and stem cell fields, aiming to arrest disease progression, restore spine and joint function, and promote long-term tissue regeneration. He employs novel large and small animal models to study disease etiology and evaluate therapeutics, working within a multidisciplinary team of biologists, bioengineers, clinicians, and veterinarians.

Research topics

• Medicine
• Biomedical engineering
• Materials science
• Biology
• Anatomy

Selected publications

• Inflammatory cytokine and catabolic enzyme expression in a goat model of intervertebral disc degeneration

  Journal of Orthopaedic Research® · 2020-02-24 · 46 citations

  articleOpen accessSenior authorCorresponding

  Intervertebral disc degeneration is implicated as a leading cause of low back pain. Persistent, local inflammation within the disc nucleus pulposus (NP) and annulus fibrosus (AF) is an important mediator of disc degeneration and negatively impacts the performance of therapeutic stem cells. There is a lack of validated large animal models of disc degeneration that recapitulate clinically relevant local inflammation. We recently described a goat model of disc degeneration in which increasing doses…

  PublisherOA PDFDOI

• Combined Hydrogel and Mesenchymal Stem Cell Therapy for Moderate-Severity Disc Degeneration in Goats

  Tissue Engineering Part A · 2020-06-17 · 45 citations

  articleOpen accessSenior authorCorresponding

  Intervertebral disc degeneration is a cascade of cellular, structural, and biomechanical changes that is strongly implicated as a cause of low-back pain. Current treatment strategies have poor long-term efficacy as they seek only to alleviate symptoms without preserving or restoring native tissue structure and function. The objective of this study was to evaluate the efficacy of a combined triple interpenetrating network hydrogel (comprising dextran, chitosan, and teleostean) and mesenchymal ste…

  PublisherOA PDFDOI

• Single cell <scp>RNA</scp> sequencing reveals emergent <scp>notochord‐derived</scp> cell subpopulations in the postnatal nucleus pulposus

  The FASEB Journal · 2023-12-12 · 8 citations

  articleOpen accessSenior authorCorresponding

  Intervertebral disc degeneration is a leading cause of chronic low back pain. Cell-based strategies that seek to treat disc degeneration by regenerating the central nucleus pulposus (NP) hold significant promise, but key challenges remain. One of these is the inability of therapeutic cells to effectively mimic the performance of native NP cells, which are unique amongst skeletal cell types in that they arise from the embryonic notochord. In this study, we use single cell RNA sequencing to demons…

  PublisherOA PDFDOI

• In Vivo Measurements Reveal Increased Nucleus Pulposus Lactate and Oxygen Concentrations in a Goat Model of Intervertebral Disc Degeneration

  JOR Spine · 2025-05-27 · 4 citations

  articleOpen accessCorresponding

  Introduction: Intervertebral disc degeneration is strongly implicated as a cause of low back pain. Although the precise pathophysiological mechanisms remain elusive, perturbations in nutrition that adversely impact the cellular microenvironment of the central nucleus pulposus (NP) may be contributing factors. A comprehensive understanding of this microenvironment, including changes in nutrient availability as a function of degeneration, is critical for the development of effective cell-based tre…

  PublisherOA PDFDOI

• Single Cell RNA Sequencing Reveals Emergent Notochord-Derived Cell Subpopulations in the Postnatal Nucleus Pulposus

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-05-22 · 4 citations

  preprintOpen accessSenior authorCorresponding

  Intervertebral disc degeneration is a leading cause of chronic low back pain. Cell-based strategies that seek to treat disc degeneration by regenerating the central nucleus pulposus hold significant promise, but key challenges remain. One of these is the inability of therapeutic cells to effectively mimic the performance of native nucleus pulposus cells, which are unique amongst skeletal cell types in that they arise from the embryonic notochord. In this study we use single cell RNA sequencing t…

  PublisherOA PDFDOI

Recent grants

• Dynamic heterogeneity of nucleus pulposus cells from development to degeneration

  NIH · $391k · 2021–2024

• Bioactive Injectable Implants for Functional Intervertebral Disc Regeneration

  NIH · 2026–2029

• Mechanisms of Vertebral Bone Disease in Mucopolysaccharidosis VII

  NIH · $240k · 2014–2018

Frequent coauthors

• Beth S. Slomine

  Kennedy Krieger Institute

  180 shared

• Frank W. Moler

  University of Michigan–Ann Arbor

  144 shared

• James R. Christensen

  Johns Hopkins University

  144 shared

• Richard Holubkov

  University of Utah

  144 shared

• J. Michael Dean

  University of Utah

  108 shared

• Faye S. Silverstein

  University of Michigan–Ann Arbor

  108 shared

• Robert L. Mauck

  Philadelphia VA Medical Center

  95 shared

• M. Nyc

  Children's Hospital of Philadelphia

  72 shared

Education

• Ph.D., Pathology

  University of Adelaide

  2008

• B.E., Mechatronic Engineering

  University of Adelaide

  2001

Similar researchers at University of Pennsylvania

• X. Sherry Liuh-47
• Andrew F. Kuntzh-22