Related Experiment Video

Updated: Apr 18, 2026

Prospective, Randomized, and Controlled Study of a Human Umbilical Cord Mesenchymal Stem Cell Injection for Treating Diabetic Foot Ulcers
04:09

Prospective, Randomized, and Controlled Study of a Human Umbilical Cord Mesenchymal Stem Cell Injection for Treating Diabetic Foot Ulcers

Published on: March 3, 2023

4.1K

Diabetes reduces mesenchymal stem cells in fracture healing through a TNFα-mediated mechanism

Kang I Ko1, Leila S Coimbra2, Chen Tian1

  • 1Department of Periodontics, University of Pennsylvania, 240 S 40th St, Levy 122 Philadelphia, PA19104, USA.

Diabetologia
|January 8, 2015
PubMed
Abstract

Insights

Diabetes impairs fracture healing by increasing TNFα, which reduces mesenchymal stem cell (MSC) numbers. Inhibiting TNFα preserves MSCs and enhances healing potential in diabetic patients.

Area of Science:

  • Biomedical Science
  • Regenerative Medicine
  • Orthopedics

Background:

  • Diabetes mellitus is a metabolic disorder that negatively impacts bone health and fracture repair.
  • Mesenchymal stem cells (MSCs) play a critical role in the complex process of fracture healing.
  • Elevated levels of tumor necrosis factor-alpha (TNFα) are observed in diabetic complications.

Purpose of the Study:

  • To investigate the effect of diabetes on MSCs during long bone fracture repair.
  • To elucidate the role of TNFα in diabetes-induced MSC dysfunction.
  • To assess the therapeutic potential of TNFα inhibition in diabetic fracture healing.

Main Methods:

  • A type 1 diabetes mouse model was established using streptozotocin.
  • Fractures were induced, and animals were treated with insulin or a TNFα inhibitor (pegsunercept).
  • MSCs were identified, and their proliferation and apoptosis were quantified using specific markers and assays (Ki67, TUNEL). In vitro studies utilized C3H10T1/2 and human bone marrow-derived MSCs with FOXO1 siRNA.

Main Results:

  • Diabetes significantly increased TNFα levels and decreased MSC numbers in fracture calluses.
  • Insulin or pegsunercept treatment restored MSC numbers to normal levels.
  • TNFα inhibition in diabetic mice increased MSC proliferation and decreased apoptosis, improving fracture healing. In vitro, TNFα induced MSC apoptosis and inhibited proliferation, effects mitigated by silencing FOXO1.

Conclusions:

  • Diabetes-induced elevation of TNFα is a key factor in reducing MSC numbers during fracture healing.
  • TNFα negatively impacts MSCs by promoting apoptosis and reducing proliferation, partly through FOXO1 regulation.
  • Targeting TNFα activity presents a promising strategy to preserve MSCs and enhance fracture healing in diabetic individuals.

More Related Videos

A Protocol for Constructing a Rat Wound Model of Type 1 Diabetes05:18

A Protocol for Constructing a Rat Wound Model of Type 1 Diabetes

Published on: February 17, 2023

6.5K
Real-Time Imaging of CCL5-Induced Migration of Periosteal Skeletal Stem Cells in Mice06:10

Real-Time Imaging of CCL5-Induced Migration of Periosteal Skeletal Stem Cells in Mice

Published on: September 16, 2020

2.7K

Related Concept Videos

Tissue Renewal without Stem Cells01:23

Tissue Renewal without Stem Cells

After cellular or tissue damage, the resident stem cells present in the human body can locally repair and regenerate the damaged tissue or organ. However, even though some tissues do not have stem cells, they can repair and regenerate with the help of pre-existing cells. For example, beta cells of the pancreas and hepatocytes of the liver can divide to renew and regenerate the tissue. Here, both cell division and cell death are well regulated by homeostasis.
However, failure of such a system...
2.3K
Mesenchymal Stem Cells01:19

Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into most connective tissue cell types, except for hematopoietic cells, depending upon the source of MSCs. For example, bone-marrow-derived MSCs (BM-MSCs) can differentiate into osteocytes, hepatocytes, and pancreatic and neuronal cells. MSCs can be isolated from various sources such as bone marrow, placenta, adipose tissue, teeth, and Wharton’s jelly, a gelatinous substance in the umbilical cord. The ease of their...
6.1K
Diabetic Foot Ulcer01:31

Diabetic Foot Ulcer

Definition A diabetic foot ulcer (DFU) is a chronic, non-healing wound that develops in individuals with diabetes. It typically occurs on pressure-bearing areas such as the heel, metatarsal heads, or hallux, and carries a high risk of infection and amputation.Pathophysiology • The development of DFUs can be explained by four interconnected mechanisms: neuropathy, ischemia, infection, and impaired wound healing. • Neuropathy is the most common factor. Sensory...
1
Psychoneuroimmunology: Diabetes and Cancer01:19

Psychoneuroimmunology: Diabetes and Cancer

Chronic stress has been linked to both the onset and progression of serious health conditions, including Type 2 diabetes and cancer. Type 2 diabetes, a widespread chronic illness, is closely associated with obesity and insulin resistance, both of which often worsen under stress. Studies indicate that men experiencing high levels of chronic stress face a 45% higher risk of developing diabetes compared to those with minimal stress. Stress triggers physiological responses that elevate blood...
655
Type I Diabetes II: Pathophysiology01:26

Type I Diabetes II: Pathophysiology

Type 1 diabetes mellitus arises from an immune-mediated destruction of pancreatic β-cells, resulting in an absolute deficiency of insulin. This process develops in genetically susceptible individuals when autoimmunity, environmental exposures, and immunologic dysregulation converge to trigger a targeted attack on the insulin-producing cells of the pancreas. The β-cells are located within the islets of Langerhans and are essential for regulating blood glucose by facilitating cellular...
1
Stem Cell Niche01:26

Stem Cell Niche

The stem cell niche is the dynamic microenvironment where stem cells reside. Inside these niches, the cells may remain undifferentiated, undergo high self-renewal, or become lineage-specific progenitors. Stem cells coexist with other niche cells, such as stromal cells. They also interact closely with the ECM. Cell-cell and cell-matrix communication occur via adhesion molecules or soluble factors that signal the stem cells and determine their fate. Stromal cells also provide survival signals to...
6.7K