Stromal Progenitor Cells in Mitigation of Non-hematopoietic Radiation Injuries

Shilpa Kulkarni, Timothy C. Wang, Chandan Guha

Research output: Contribution to journalReview article

2 Citations (Scopus)

Abstract

Purpose of Review: Therapeutic exposure to high doses of radiation can severely impair organ function due to ablation of stem cells. Normal tissue injury is a dose-limiting toxicity for radiation therapy (RT). Although advances in the delivery of high-precision conformal RT has increased normal tissue sparing, mitigating and therapeutic strategies that could alleviate early and chronic radiation effects are urgently needed in order to deliver curative doses of RT, especially in abdominal, pelvic, and thoracic malignancies. Radiation-induced gastrointestinal injury is also a major cause of lethality from accidental or intentional exposure to whole-body irradiation in the case of nuclear accidents or terrorism. This review examines the therapeutic options for mitigation of non-hematopoietic radiation injuries. Recent Findings: We have developed stem cell-based therapies for the mitigation of acute radiation syndrome and radiation-induced gastrointestinal syndrome. This is a promising option because of the robustness of standardized isolation and transplantation of stromal cell protocols, and their ability to support and replace radiation-damaged stem cells and stem cell niche. Stromal progenitor cells (SPC) represent a unique multipotent and heterogeneous cell population with regenerative, immunosuppressive, anti-inflammatory, and wound-healing properties. SPC are also known to secrete various key cytokines and growth factors such as platelet-derived growth factors, keratinocyte growth factor, R-spondins, and may consequently exert their regenerative effects via paracrine function. Additionally, secretory vesicles such as exosomes or microparticles can potentially be a cell-free alternative replacing the cell transplant in some cases. Summary: This review highlights the beneficial effects of SPC on tissue regeneration with their ability to (a) target the irradiated tissues, (b) recruit host stromal cells, (c) regenerate endothelium and epithelium, (d) and secrete regenerative and immunomodulatory paracrine signals to control inflammation, ulceration, wound healing, and fibrosis.

Original languageEnglish (US)
Pages (from-to)221-230
Number of pages10
JournalCurrent Pathobiology Reports
Volume4
Issue number4
DOIs
StatePublished - Dec 1 2016

Fingerprint

Radiation Injuries
Stromal Cells
Stem Cells
Radiation
Radiotherapy
Wound Healing
Acute Radiation Syndrome
Radioactive Hazard Release
Fibroblast Growth Factor 7
Exosomes
Stem Cell Niche
Terrorism
Whole-Body Irradiation
Platelet-Derived Growth Factor
Radiation Effects
Wounds and Injuries
Secretory Vesicles
Immunosuppressive Agents
Cell- and Tissue-Based Therapy
Endothelium

Keywords

  • Epithelial regeneration
  • Exosomes
  • Growth factors
  • Inflammation
  • Intestinal stem cells
  • Radiation-induced gastrointestinal diseases
  • Stromal progenitor cells
  • Vascularization

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Pathology and Forensic Medicine
  • Cancer Research

Cite this

Stromal Progenitor Cells in Mitigation of Non-hematopoietic Radiation Injuries. / Kulkarni, Shilpa; Wang, Timothy C.; Guha, Chandan.

In: Current Pathobiology Reports, Vol. 4, No. 4, 01.12.2016, p. 221-230.

Research output: Contribution to journalReview article

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abstract = "Purpose of Review: Therapeutic exposure to high doses of radiation can severely impair organ function due to ablation of stem cells. Normal tissue injury is a dose-limiting toxicity for radiation therapy (RT). Although advances in the delivery of high-precision conformal RT has increased normal tissue sparing, mitigating and therapeutic strategies that could alleviate early and chronic radiation effects are urgently needed in order to deliver curative doses of RT, especially in abdominal, pelvic, and thoracic malignancies. Radiation-induced gastrointestinal injury is also a major cause of lethality from accidental or intentional exposure to whole-body irradiation in the case of nuclear accidents or terrorism. This review examines the therapeutic options for mitigation of non-hematopoietic radiation injuries. Recent Findings: We have developed stem cell-based therapies for the mitigation of acute radiation syndrome and radiation-induced gastrointestinal syndrome. This is a promising option because of the robustness of standardized isolation and transplantation of stromal cell protocols, and their ability to support and replace radiation-damaged stem cells and stem cell niche. Stromal progenitor cells (SPC) represent a unique multipotent and heterogeneous cell population with regenerative, immunosuppressive, anti-inflammatory, and wound-healing properties. SPC are also known to secrete various key cytokines and growth factors such as platelet-derived growth factors, keratinocyte growth factor, R-spondins, and may consequently exert their regenerative effects via paracrine function. Additionally, secretory vesicles such as exosomes or microparticles can potentially be a cell-free alternative replacing the cell transplant in some cases. Summary: This review highlights the beneficial effects of SPC on tissue regeneration with their ability to (a) target the irradiated tissues, (b) recruit host stromal cells, (c) regenerate endothelium and epithelium, (d) and secrete regenerative and immunomodulatory paracrine signals to control inflammation, ulceration, wound healing, and fibrosis.",
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