osteoclast-derivation-from-mouse-bone-marrow

Osteoclast Derivation from Mouse Bone Marrow

Osteoclasts are highly specialized cells that are derived from the monocyte/macrophage lineage of the bone marrow. Their unique ability to resorb both the ...

isolation-enrichment-human-adipose-derived-stromal-cells-for-enhanced

Isolation and Enrichment of Human Adipose-derived Stromal Cells for Enhanced Osteogenesis

Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are considered the gold standard for stem cell-based tissue engineering applications. However, the ...

a-mouse-fetal-skin-model-of-scarless-wound-repair

A Mouse Fetal Skin Model of Scarless Wound Repair

Early in utero, but not in postnatal life, cutaneous wounds undergo regeneration and heal without formation of a scar. Scarless fetal wound healing occurs ...

murine-dermal-fibroblast-isolation-by-facs

Murine Dermal Fibroblast Isolation by FACS

Fibroblasts are the principle cell type responsible for secreting extracellular matrix and are a critical component of many organs and tissues. Fibroblast ...

Creation of Abdominal Adhesions in Mice

Abdominal adhesions consist of fibrotic tissue that forms in the peritoneal space in response to an inflammatory insult, typically surgery or ...

rapid-isolation-bmpr-ib-adipose-derived-stromal-cells-for-use

Rapid Isolation of BMPR-IB+ Adipose-Derived Stromal Cells for Use in a Calvarial Defect Healing Model

Invasive cancers, major injuries, and infection can cause bone defects that are too large to be reconstructed with preexisting bone from the patient's own ...

Stanford University School of Medicine

University of Hawai'i

In 2006, Dr. Yamanaka created the induced pluripotent stem cell (iPSC) by reprogramming adult fibroblasts back to an immature, pluripotent state. Effectively bypassing the ethical constraints of human embryonic stem cells, iPSCs have expanded the horizons of regenerative medicine by offering a means to derive autologous patient-matched cells and tissues for clinical transplantation. However, persisting safety concerns must be addressed prior to their widespread clinical application. In this review, we discuss the history of iPSCs, derivation strategies, and current research involving gene therapy and disease modeling. We review the potential of iPSCs for improving a range of cell-based therapies and obstacles to their clinical implementation.

Induced pluripotent stem cells in regenerative medicine and disease modeling.

Fat grafting has become increasingly popular for the correction of soft-tissue deficits at many sites throughout the body. Long-term outcomes, however, depend on delivery of fat in the least traumatic fashion to optimize viability of the transplanted tissue. In this study, the authors compare the biological properties of fat following injection using two methods.

Studies in fat grafting: Part I. Effects of injection technique on in vitro fat viability and in vivo volume retention.

Hypoxia-inducible factor (HIF)-1α, part of the heterodimeric transcription factor that mediates the cellular response to hypoxia, is critical for the expression of multiple angiogenic growth factors, cell motility, and the recruitment of endothelial progenitor cells. Inhibition of the oxygen-dependent negative regulator of HIF-1α, prolyl hydroxylase domain-2 (PHD-2), leads to increased HIF-1α and mimics various cellular and physiological responses to hypoxia. The roles of PHD-2 in the epidermis and dermis have not been clearly defined in wound healing.

Epidermal or dermal specific knockout of PHD-2 enhances wound healing and minimizes ischemic injury.

Early fetuses heal wounds without the formation of a scar. Many studies have attempted to explain this remarkable phenomenon. However, the exact mechanism remains unknown. Herein, we examine the predominant cell types of the epidermis and dermis--the keratinocyte and fibroblast--during different stages of fetal development to better understand the changes that lead to scarring wound repair versus regeneration.

Gene expression in fetal murine keratinocytes and fibroblasts.

Wound healing is a highly evolved defense mechanism against infection and further injury. It is a complex process involving multiple cell types and biological pathways. Mammalian adult cutaneous wound healing is mediated by a fibroproliferative response leading to scar formation. In contrast, early to mid-gestational fetal cutaneous wound healing is more akin to regeneration and occurs without scar formation. This early observation has led to extensive research seeking to unlock the mechanism underlying fetal scarless regenerative repair. Building upon recent advances in biomaterials and stem cell applications, tissue engineering approaches are working towards a recapitulation of this phenomenon. In this review, we describe the elements that distinguish fetal scarless and adult scarring wound healing, and discuss current trends in tissue engineering aimed at achieving scarless tissue regeneration.

Tissue engineering and regenerative repair in wound healing.

Significance: Poor wound healing remains a significant health issue for a large number of patients in the United States. The physiologic response to local wound hypoxia plays a critical role in determining the success of the normal healing process. Hypoxia-inducible factor-1 (HIF-1), as the master regulator of oxygen homeostasis, is an important determinant of healing outcomes. HIF-1 contributes to all stages of wound healing through its role in cell migration, cell survival under hypoxic conditions, cell division, growth factor release, and matrix synthesis throughout the healing process. Recent Advances: Positive regulators of HIF-1, such as prolyl-4-hydroxylase inhibitors, have been shown to be beneficial in enhancing diabetic ischemic wound closure and are currently undergoing clinical trials for treatment of several human-ischemia-based conditions. Critical Issues: HIF-1 deficiency and subsequent failure to respond to hypoxic stimuli leads to chronic hypoxia, which has been shown to contribute to the formation of nonhealing ulcers. In contrast, overexpression of HIF-1 has been implicated in fibrotic disease through its role in increasing myofibroblast differentiation leading to excessive matrix production and deposition. Both positive and negative regulators of HIF-1 therefore provide important therapeutic targets that can be used to manipulate HIF-1 expression where an excess or deficiency in HIF-1 is known to correlate with pathogenesis. Future Directions: Targeting HIF-1 during wound healing has many important clinical implications for tissue repair. Counteracting the detrimental effects of excessive or deficient HIF-1 signaling by modulating HIF-1 expression may improve future management of poorly healing wounds.

The Role of Hypoxia-Inducible Factor in Wound Healing.

Pathophysiologic changes associated with diabetes impair new blood vessel formation and wound healing. Mesenchymal stem cells derived from adipose tissue (ASCs) have been used clinically to promote healing, although it remains unclear whether diabetes impairs their functional and therapeutic capacity.

Diabetes impairs the angiogenic potential of adipose-derived stem cells by selectively depleting cellular subpopulations.

Although fat grafting can address many soft-tissue deficits, results remain inconsistent. In this study, the authors compared physical properties of fat following injection using an automated, low-shear device or the modified Coleman technique.

Studies in fat grafting: Part II. Effects of injection mechanics on material properties of fat.

Chronic wounds are a major source of morbidity for patients and represent a significant health burden. Implementing noninvasive techniques that accelerate healing of these wounds would provide great benefit. Ultrasound appears to be an effective modality for the treatment of chronic wounds in humans. MIST Therapy is a noncontact, low-frequency ultrasound treatment delivered through a saline mist. A variety of mechanisms have been proposed to explain the efficacy of ultrasound therapy, but the underlying molecular and cellular pathways impacted by this technique remain unclear. The in vivo effect of noncontact, low-frequency ultrasound was therefore examined in a humanized excisional wound model.

Noncontact, low-frequency ultrasound therapy enhances neovascularization and wound healing in diabetic mice.

Adipose derived stromal cells obtained by ultrasound assisted liposuction versus suction assisted liposuction: a comparison of their regenerative capacity.

Key transcriptional differences exist in diabetic fracture healing.

Current methods for the isolation of fibroblasts require extended ex vivo manipulation in cell culture. As a consequence, prior studies investigating fibroblast biology may fail to adequately represent cellular phenotypes in vivo. To overcome this problem, we describe a detailed protocol for the isolation of fibroblasts from the dorsal dermis of mice that bypasses the need for cell culture thereby preserving the physiologic transcriptional and proteomic profiles of each cell. Using the described protocol we characterized the transcriptional programs and the surface expression of 176 CD markers in cultured vs. uncultured fibroblasts. The differential expression patterns we observed highlight the importance of a live harvest for investigations of fibroblast biology.

ArticleTotal : 6	Year
Publication title Cited by 30	2014
Publication title Cited by 11	2015
Publication title Cited by 24	2015
Publication title Cited by 28	2016
Publication title Cited by 9	2016

Article	Year
Induced pluripotent stem cells in regenerative medicine and disease modeling. Current stem cell research & therapy\| PubMed ID: 24359141	2014
Studies in fat grafting: Part I. Effects of injection technique on in vitro fat viability and in vivo volume retention. Plastic and reconstructive surgery\| PubMed ID: 24622574	2014
Epidermal or dermal specific knockout of PHD-2 enhances wound healing and minimizes ischemic injury. PloS one\| PubMed ID: 24695462	2014
Gene expression in fetal murine keratinocytes and fibroblasts. The Journal of surgical research\| PubMed ID: 24726057	2014
Tissue engineering and regenerative repair in wound healing. Annals of biomedical engineering\| PubMed ID: 24788648	2014
The Role of Hypoxia-Inducible Factor in Wound Healing. Advances in wound care\| PubMed ID: 24804159	2014
Diabetes impairs the angiogenic potential of adipose-derived stem cells by selectively depleting cellular subpopulations. Stem cell research & therapy\| PubMed ID: 24943716	2014
Studies in fat grafting: Part II. Effects of injection mechanics on material properties of fat. Plastic and reconstructive surgery\| PubMed ID: 25028817	2014
Noncontact, low-frequency ultrasound therapy enhances neovascularization and wound healing in diabetic mice. Plastic and reconstructive surgery\| PubMed ID: 25158717	2014
Adipose derived stromal cells obtained by ultrasound assisted liposuction versus suction assisted liposuction: a comparison of their regenerative capacity. Plastic and reconstructive surgery\| PubMed ID: 25254755	2014
Key transcriptional differences exist in diabetic fracture healing. Plastic and reconstructive surgery\| PubMed ID: 25254763	2014
Live Fibroblast Harvest Reveals Surface Marker Shift in vitro. Tissue engineering. Part C, Methods\| PubMed ID: 25275778	2014

Michael S. Hu

Biography

JoVE Journal Publications

Other Publications