Keratinocyte Induced Differentiation of Mesenchymal Stem Cells into Dermal Myofibroblasts: A Role in Effective Wound Healing

Authors

  • Pravin J. Mishra Intermountain Precision Genomics, Intermountain Healthcare, Dixie Regional Medical Center 292 South 1470 East, Suite 201 & 301, St. George, UT 84770, USA
  • Prasun J. Mishra Department of Biochemical and Cellular Pharmacology, Genentech, 1, DNA Way, South San Francisco, California 94080, USA
  • Debabrata Banerjee Department of Pharmacology, Robert Wood Johnson Medical School, Graduate School of Biomedical Sciences, New Brunswick-Piscataway, Rutgers University, 675 Hoes Lane West, Piscataway, NJ 08854. USA

DOI:

https://doi.org/10.13052/ijts2246-8765.2016.002

Keywords:

Mesenchymal stem cells, keratinocyte conditioned medium, dermal myofibroblast, cytokine secretion, wound healing, scarring, animal models

Abstract

We have previously demonstrated that human mesenchymal stem cells (hMSCs) migrate toward human keratinocytes as well as toward conditioned medium from cultured human keratinocytes (KCM) indicating that the hMSCs respond to signals from keratinocytes [1]. Using fluorescently labeled cells we now show that in vitro hMSCs appear to surround keratinocytes, and this organization is recapitulated in vivo. Incubation of hMSCs with KCM induced dermal myofibroblast like differentiation characterized by expression of cytoskeletal markers and increased expression of cytokines including SDF-1, IL-8, IL-6 and CXCL5. Interaction of keratinocytes with hMSCs appears to be important in the wound healing process. Therapeutic efficacy of hMSCs in wound healing was examined in two animal models representing normal and chronic wound healing. Accelerated wound healing was observed when hMSCs and KCM exposed hMSCs (KCMSCs) were injected near wound site in nude and NOD/SCID mice. Long term follow up of wound healing revealed that in the hMSC treated wounds there was little evidence of residual scarring. These dermal myofibroblast like hMSCs add to the wound healing process. Together, the keratinocyte and hMSCs morphed dermal myofibroblast like cells as well as the factors secreted by these cells support wound healing with minimal scarring. The ability of hMSCs to support wound healing process represents another striking example of the importance of keratinocyte and hMSCs interplay in the wound microenvironment resulting in effective wound healing with minimal scarring.

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Author Biographies

Pravin J. Mishra, Intermountain Precision Genomics, Intermountain Healthcare, Dixie Regional Medical Center 292 South 1470 East, Suite 201 & 301, St. George, UT 84770, USA

Pravin J. Mishra is an oncology thought leader trained from National Cancer Institute (NCI), National Institutes of Health (NIH). He currently serves as laboratory director and research and development director of Intermountain precision genomics, a leading precision medicine organization in the nation.At Intermountain precision genomics, he oversees omics laboratory operations and is leading the cutting edge discovery and innovation efforts in precision medicine and oncology. He earned his Ph.D. in Molecular Medicine and Oncology from The George Washington University, Washington, DC. Dr. Mishra has developed subject expertise in oncology, stem cells, cancer genomics, drug discovery, and developmental therapeutics. His research efforts at NIH led to the discovery of signature biomarkers that can predict late stage melanoma patient survival, and clinically could save multiple lives. Dr. Mishra has received numerous accolades, including prestigious National Cancer Institute-Directors Award, awarded by Nobel laureate Dr. Harold Varmus, research excellence award by NIH, technology transfer award by NIH, outstanding research award by NIH Director and honored by several other esteemed organizations including AACR. Dr. Mishra is founder of OncoTelligent, a non-profit organization providing scientific evidence and support to cancer patients and family members for disease prevention, cure and healing. Dr. Mishra is known for his unconventional perspective and has authored several international studies and patents. Dr. Mishra’s scientific goal is to develop and support technologies and strategies to fight and cure cancer. His research in the area of precision genomics and cancer has not only contributed to understanding of underlying cancer biology but also has saved many lives. Dr. Mishra has selflessly helped several cancer patients and their family members.

Prasun J. Mishra, Department of Biochemical and Cellular Pharmacology, Genentech, 1, DNA Way, South San Francisco, California 94080, USA

Prasun J. Mishra Ph.D. is a scientist at Genentech, where his research is primarily focused on developing ‘lifesaving’ next-generation personalized anti-cancer drugs. He has over 15 years of experience in managing multidisciplinary translational research teams with a successful track record of driving drugs/drug-combinations from research through clinical development. The significance of his research has been recognized in numerous awards, honors and lectureships, including prestigious NIH Earl Stadtman Lectureships, Thompson Reuters Lectureship, Federal Technology Transfer Awards and NCI Director’s Innovation Awards. Discoveries lead by him and his teams have contributed to the development of new and viable strategies of prevention, diagnosis and treatment of cancer patients in the clinic. He earned his Ph.D. degree in Pharmacology from Rutgers University, NJ and a postdoctoral fellowship from National Institutes of Health (NIH), Bethesda, MD. Before moving to Genentech he served as a principal investigator at National Cancer Institute (NCI) on two peer-reviewed NCI/NIH-funded grants focused on developing improved anti-cancer therapy. He has also served as a non-dilutive funding adviser to accelerate commercialization and helped organizations to compete for over $30 billion available funds in non-dilutive federal R&D funding. He also serves on the advisory board of California Life Sciences Association (CLSA), the leading voice for California’s life sciences sector to help grow California’s life sciences innovation ecosystem. Moreover, his passion for translational research has resulted in over 100 presentations/publications including 5 US patents, 5 federal technology transfer awards and 7 drugs/drug combinations in clinical trials.

Debabrata Banerjee, Department of Pharmacology, Robert Wood Johnson Medical School, Graduate School of Biomedical Sciences, New Brunswick-Piscataway, Rutgers University, 675 Hoes Lane West, Piscataway, NJ 08854. USA

D. Banerjee is an Associate Professor of Pharmacology and Assistant Dean for Global Initiatives at Rutgers Graduate School of Biomedical Sciences. He has published over 100 peer reviewed research papers in esteemed journals. He holds six US patents and has trained several students including postdoctoral fellows, doctoral and masters’ students and research technicians.

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Published

2016-04-17

How to Cite

Mishra, P. J., Mishra, P. J., & Banerjee, D. (2016). Keratinocyte Induced Differentiation of Mesenchymal Stem Cells into Dermal Myofibroblasts: A Role in Effective Wound Healing. International Journal of Translational Science, 2016, 5–32. https://doi.org/10.13052/ijts2246-8765.2016.002

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Volume 2016

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