Laboratory for Regenerative Medicine & Applied Sciences
The long-term goal of The Laboratory for Regenerative Medicine and Applied Sciences is to develop a functional hybrid graft to heal full thickness skin defects and explore the potential of epithelial derived stem cells (LGR5+ and LGR6+) for burns, neuropathic ulcers, and hair regeneration.
We are also exploring the potential of merging TRAIL therapy with conventional breast reconstruction procedures to eliminate breast cancer recurrence after mastectomy.
Current Research Projects
- Bioengineered Skin: An Approach To Heal Full Thickness Skin Defects
Goal: To develop a three dimensional (3-D) full thickness bioengineered skin to heal full thickness skin defects by providing complete closure and protection of wounds, with augmented wound healing and neovascularization at the injury site along with the development of nascent hair follicles.
- Human Hair Regeneration: A Cure for Male Pattern Baldness
Goal: To produce de novo human hair follicles from LGR5 stem cells for a potential long term treatment for male pattern baldness.
- A Microbiologic Comparison of Acellular Dermal Matrices as an Aseptic Reconstructive Material and a Scaffold for Stem Cell In- growth
Goal: To perform a microbiologic assessment of different Acellular Dermal Matrices (ADM) that are commonly used during reconstructive surgeries
- The TRAIL Flap: Bridging the Gap Between Breast Cancer Treatment and Reconstruction via a Gene Therapy Flap
Goal: To determine if the TRAIL flap will be able to deliver anti-cancer therapy to a local tumor bed, which will limit systemic side effects.
- Development of a Chimeric Free Flap for Soft Tissue Coverage Following Burns, Trauma, Chronic Wounds and Cancer Resection
Goal: To pursue clinical use of epithelial stem cells in chronic wounds, burns and poly-trauma and develop a method of soft tissue coverage utilizing chimeric free flap allografts.
- Therapeutic Fat Grafting: Breast Cancer Treatment and Reconstruction
Goal: To determine the oncological safety of lipofilling/fat grafting.
- ADSC Potentiates Tissue Reorganization/Repair – Radiated Expansion
Goal: To measure the effects of irradiation on tissue regeneration by evaluating ADSC differentiation into regenerative skin components and quantifying ADSC paracrine secretion of growth hormones.
Published Work Highlighting The Tissue Engineering Efforts Of The Basic Science Lab In The Institute For Plastic Surgery.
- Lough DM, Yang M, Blum A, Reichensperger JD, Cosenza NM, Wetter N, Cox LA, Harrison CE, Neumeister MW. Transplantation of the LGR6+ Epithelial Stem Cell Into Full-Thickness Cutaneous Wounds Results in Enhanced Healing, Nascent Hair Follicle Development, and Augmentation of Angiogenic Analytes. Plast Reconstr Surg. 2014 MAR;133(3):579-90 DOI:10.1097/PRS. 0000000000000075. PubMed PMID: 24572851.
The specific aim of the experiments in the above publication was to demonstrate the ability of LGR6+ (a subset of epithelial stem cells) as a stem cell based therapy to regenerate full thickness functional skin in a burn model.
This study showed that LGR6+ cells promote epithelialization, hair growth, and angiogenesis.
These findings suggest a potential role for epithelial stem cells in autologous and allogenic cell transplantation.
Additional experiments are currently being done to test the ability of these cells to treat other types of wounds including radiation.
Epithelial stem cells are also currently being used to test their ability to regenerate hair follicles in a model of male pattern baldness.
- Derby BM, Dai H, Reichensperger J, Cox L, Harrison C, Cosenza N, Yang M, Bueno RA, Neumeister MW. Adipose-Derived Stem Cell to Epithelial Stem Cell Transdifferentiation: A Mechanism to Potentially Improve Understanding of Fat Grafting’s Impact on Skin Rejuvenation. Aesthet Surg J. 2014 Jan 1;34(1):142-53. DOI: 10.1177/1090820X13515700. Epub 2013 Dec 12. PubMed PMID: 24334307.
The specific aim of the experiments in the above publication was to demonstrate adipose derived stem cells’ ability to differentiate in to cell lineages of the skin.
The adipose derived stem cells injected in to the subdermal plane displayed a cell surface marker for epithelial stem cells (p63) at the endpoint of the experiment. These findings indicated that adipose derived stem cells may possess the ability to transdifferentiate into epithelial stem cells.
Additional experiments are currently being done to understand the mechanism of the differentiation and further classify the injected cells.
- Lough DM, Yang M, Blum A, Reichensperger JD, Cosenza NM, Wetter N, Cox LA, Harrison CE, Neumeister MW. Transplantation of the LGR6+ epithelial stem cell into full-thickness cutaneous wounds results in enhanced healing, nascent hair follicle development, and augmentation of angiogenic analytes. Plast Reconstr Surg. 2014 Mar;133(3):579-90. doi: 10.1097/PRS.0000000000000075.
- Lough D, Dai H, Yang M, Reichensperger J, Cox L, Harrison C, Neumeister MW. Stimulation of the Follicular Bulge LGR5+ and LGR6+ Stem Cells with the Gut-Derived Hman Alpha Defensin 5 Results in Deceased Bacterial Presence, Enhanced Wound Healing, and Hair Growth from Tissue Devoid of Adnexal Structures. Plast Reconstr Surg 2013 Nov 132(5):1159-1171.
- Liu G, Neumeister MW, Reichensperger J, Yang RD. Therapeutic potential of human adipose stem cells in a cancer stem cell-like gastric cancer cell model. Int J Oncol 2013 oct;43($): 1301-9.
- Derby BM, Reichensperger J, Chambers C, Bueno RA, Suchy H, Neumeister MW. Early Growth Response Factor-1: Expression in a Rabbit Flexor Tendon Scar Model. Pla Reconstr Surg 2012 Mar;129(3):435e-442e.
- Roth V, Herron MS, Bueno RA, Chambers CB, Neumeister MW. Stimulating AAngiogenesis by Hyperbaric Oxygen in an Isolated Tissue Construct. Undersea Hyperb Med 2011 Nov-Dec 38(6):509-14.
- Cooney, DS, Chambers CB, Suchy H, Hornick MC, Reichensperger J, Neumeister MW. Transgene Expression in a Model of Composite Tissue Allotransplantation. Plast Reconstr Surg 2010 Mar: 125(3): 837-845.
Research Staff & Faculty
Michael W. Neumeister, MD, FRCSC, FACS
Ashim Gupta, MS, PhD
Carrie Harrison, BS
Lisa Cox, BS
Joel Reichensperger, BS