The Paracrine Activity and Differentiation Potential of Human Adipose-Derived Stem Cells Can Be Influenced by Age.

The Paracrine Activity and Differentiation Potential of Human Adipose-Derived Stem Cells Can Be Influenced by Age.

Stem cell therapy has been increasingly used as a therapeutic option in the treatment of numerous diseases, including many inflammatory and vascular diseases.  

The primary sources of stem cells are bone marrow (BM), dental tissue, adipose tissue, and umbilical cord blood; BM is considered the primary source of multipotent stem cells. While BM is an important source of stem cells for clinical cellular therapy, BM cell culture is an invasive procedure that presents both a potential risk and burden to patients. 

Considering this, researchers have conducted numerous studies to investigate adipose tissue as an alternative to BM. Findings indicate that adipose-derived stem cells (ADSCs) can be expanded ex vivo and possess characteristics similar to those found in BM. However, the quality of ADSCs have been found to be affected by age, underlying disease, or the lifestyle of the individual, making these factors a critical factor in estimating the efficacy of stem cell therapy.  

The purpose of Park et al.’s study was to explore the association between age and ADSC activity, including paracrine and differentiation potential; the authors hypothesized that age affects the cellular activity of ADSCs.  

To verify this hypothesis, Park et al. analyzed the essential functions of ADSCs from young and elderly donors by evaluating the cell proliferation rate, differentiation potential, and cytokine profile.

As a result of this study, the authors reported that age reduces the viability and proliferation rate of ADSCs. Specifically, the viability of ADSCs was significantly reduced in the elderly group when compared to the young group; this reduction also led to an increase in cell population doubling time. This finding led to the conclusion that ADSCs from the elderly may lose their therapeutic efficacy during ex vivo culture.

Paracrine action of ADSCs was also found to be altered by age. The authors observed that as stem cells age, they tend to lose their ability to secrete cytokines or growth factors due to senescence. Considering that transplanted stem cells primarily act through paracrine factors, reduced function resulting from age could be a critical factor in predicting their treatment efficacy after transplantation. 

Age was also found to weaken the differentiation potential of ADSCs. Age had previously been proven to influence cell repopulation rate and cytokine secretion. The authors suggest that these findings also indicate that age may disrupt the differentiation potential of ADSCs. After testing this as part of this study, the authors reported that ADSCs from the elderly group do in fact demonstrate a significant reduction in adipogenic potential when compared to the young group. 

The authors conclude that this study demonstrated that a donor’s age affects the proliferative activity, paracrine action, and differentiation potential of ADSCs and that further evaluation of ADSC based on age will be helpful for the development of ADSCs as a cellular therapeutic agent in stem cell therapy. 

Source: “Age affects the paracrine activity and differentiation potential … – NCBI.” 22 Dec. 2020, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789087/.

Researchers Effectively Treat Experimental Colitis with Fat-Derived Stem Cells

Researchers Effectively Treat Experimental Colitis with Fat-Derived Stem Cells

Crohn’s disease is a chronic illness that can affect any part of the gastrointestinal tract but mostly affects the small and large intestines. People with Crohn’s disease often have inflammation of the large bowel (Crohn’s disease is an inflammatory bowel disease or IBD). This colitis causes abdominal pain, cramping, diarrhea, along with bleeding and infections in the gastrointestinal tract. Crohn’s disease can interfere with a person’s ability to absorb nutrients, leading to malnutrition and weight loss. The medical community is debating whether it is possible to treat experimental colitis with fat-derived stem cells.

The standard medical treatment for Crohn’s disease involves one or more powerful drugs. When the disease flares up, patients usually must take steroids either orally or intravenously. They may also receive disease-modifying therapy such as immunomodulators and biologic medications. Many patients do enjoy remission once they receive these powerful drugs; however, side effects can be difficult to tolerate. Patients who cannot tolerate these powerful drugs or do not achieve disease remission may have to take steroids every day. Chronic steroid use has many severe and sometimes permanent side effects. If these treatments fail, patients may need to have surgery to remove a portion of their intestines that have been damaged by Crohn’s disease.

In an effort to find safe and effective treatments for Crohn’s disease, researchers have been testing stem cells in laboratory animals. In one study, scientists used a chemical to cause colon inflammation (colitis) in mice. This chemical causes many of the symptoms of humans with Crohn’s disease experience such as diarrhea, tissue damage, and weight loss. The researchers then treated some of the mice with mesenchymal stem cells gathered from human fat tissue (adipose) to see if stem cells could improve the symptoms.

Remarkably, human stem cell treatment reduced diarrhea, inflammation, and disease severity in mice with colitis. The chemical colitis caused mice to lose approximately 15 to 20% of their body weight. Mice that received stem cell treatment regained most of the weight they had lost. Researchers also noted that mice treated with adipose-derived mesenchymal stem cells lived significantly longer than those that did not receive stem cell treatment.

Of course, this research was performed in laboratory animals, but it lays important groundwork for testing in humans. Indeed, since the publication of this report, researchers have been able to show that adipose-derived stem cells helped patients with Crohn’s disease. This exciting work will no doubt lead to future studies that may help pave the way to wider use of stem cells in the treatment of inflammatory bowel disease, such as Crohn’s disease.

Reference: Gonzalez, M. (2009). Adipose-Derived Mesenchymal Stem Cells Alleviate Experimental Colitis by Inhibiting Inflammatory and Autoimmune Responses. Gastroenterology. Volume 136, Issue 3, March 2009, Pages 978-989

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