The application of stem cell therapy and brown adipose tissue transplantation in metabolic disorders

Lu, Kang; Dass, Kingsley Theras Primus; Lin, Shinn‐Zong; Harn, Horng‐Jyh; Liu, Shih‐Ping

doi:10.1016/j.jcyt.2020.06.004

Cited by 14 publications

(10 citation statements)

References 73 publications

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“…Brown adipocytes are characterized by the presence of a large number of mitochondria, multilocular lipid droplets, sympathetic innervations, and the expression of uncoupling protein‐1 (UCP1) which allows generating heat with little ATP production 161,165 . Brown adipose develops from paraxial mesoderm (dermomyotome) similar to muscles and dorsal dermis 166 …”

Section: Characterization Of Ad‐mscsmentioning

confidence: 99%

Adipose‐derived stromal cells for nonhealing wounds: Emerging opportunities and challenges

Deptuła

Brzezicka

Skoniecka

et al. 2021

Medicinal Research Reviews

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Wound healing complications affect thousands of people each year, thus constituting a profound economic and medical burden. Chronic wounds are a highly complex problem that usually affects elderly patients as well as patients with comorbidities such as diabetes, cancer (surgery, radiotherapy/chemotherapy) or autoimmune diseases. Currently available methods of their treatment are not fully effective, so new solutions are constantly being sought. Cell‐based therapies seem to have great potential for use in stimulating wound healing. In recent years, much effort has been focused on characterizing of adipose‐derived mesenchymal stromal cells (AD‐MSCs) and evaluating their clinical use in regenerative medicine and other medical fields. These cells are easily obtained in large amounts from adipose tissue and show a high proregenerative potential, mainly through paracrine activities. In this review, the process of healing acute and nonhealing (chronic) wounds is detailed, with a special attention paid to the wounds of patients with diabetes and cancer. In addition, the methods and technical aspects of AD‐MSCs isolation, culture and transplantation in chronic wounds are described, and the characteristics, genetic stability and role of AD‐MSCs in wound healing are also summarized. The biological properties of AD‐MSCs isolated from subcutaneous and visceral adipose tissue are compared. Additionally, methods to increase their therapeutic potential as well as factors that may affect their biological functions are summarized. Finally, their therapeutic potential in the treatment of diabetic and oncological wounds is also discussed.

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Section: Characterization Of Ad‐mscsmentioning

confidence: 99%

Adipose‐derived stromal cells for nonhealing wounds: Emerging opportunities and challenges

Deptuła

Brzezicka

Skoniecka

et al. 2021

Medicinal Research Reviews

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“…A series of studies have revealed that BAT is capable of reversing the metabolic disorders associated with obesity, 20–23 and it is an endocrine organ that may represent a therapeutic target for obesity and related diseases. However, the BAT mass in adults is low and declines with age 24–26 .…”

Section: Discussionmentioning

confidence: 99%

Skeletal muscle provides a pro‐browning microenvironment for transplanted brown adipose tissue to maintain its effect to ameliorate obesity in ob/ob mice

et al. 2021

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Brown adipose tissue (BAT) transplantation is a promising means of increasing whole‐body energy metabolism to ameliorate obesity. However, the changes in BAT following transplantation and the effects of the microenvironment of the recipient site on graft function have yet to be fully characterized. Therefore, we aimed to determine the effects of transplanting BAT from C57BL/6 mice into the dorsal subcutaneous region or deep to the quadriceps femoris muscle of leptin‐deficient ob/ob mice. Subcutaneously transplanted BAT lost features of BAT and demonstrated greater inflammatory cell infiltration and more oil cysts 16 weeks following transplantation. By contrast, the sub‐muscularly transplanted BAT maintained features of BAT and was more highly vascularized. Interestingly, sub‐muscular BAT transplantation led to a significant increase in oxygen consumption and less inflammation in subcutaneous fat, which was associated with long‐term reductions in insulin resistance and body mass gain, whereas the subcutaneous transplants failed after 16 weeks. These results demonstrate that the beneficial effects of BAT transplantation depend upon the microenvironment of the recipient site. Skeletal muscle may provide a microenvironment that maintains the inherent features of BAT grafts over a long period of time, which facilitates a reduction in obesity and improvements in glucose homeostasis.

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“…Adipose-derived stem cells have the potential to contribute to the pathophysiology of obesity and metabolic disorders due to their bioactive secretome. Due to their immunomodulatory properties, they can regulate the metabolic inflammation during obesity, and therefore can be used in the treatment of metabolic diseases [146,147]. Moreover, ASCs isolated from WAT are desired to be used in cell therapy for metabolism disorders.…”

Section: Metabolic Diseasesmentioning

confidence: 99%

“…They can be easily differentiated into brown adipocytes and this conversion is dependent on PPARγ agonist and differentiated cells express a higher level of uncoupling protein 1 (UCP1) important for adaptive thermogenesis. It has been already shown that ASCs-implanted animals demonstrated less weight gain than animals in the control group [146,148,149]. Recently, Ikemoto et al showed that ASCs isolated from diabetic and non-diabetic patients exhibit the same phenotype and can be differentiated into insulin-producing cells (IPCs) characterized by the autonomous insulin secretion.…”

Section: Metabolic Diseasesmentioning

confidence: 99%

Adipose-Derived Stem Cells Secretome and Its Potential Application in “Stem Cell-Free Therapy”

2021

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Adipose-derived stem cells (ASCs) secrete many cytokines, proteins, growth factors, and extracellular vesicles with beneficial outcomes that can be used in regenerative medicine. It has great potential, and the development of new treatment strategies using the ASCs secretome is of global interest. Besides cytokines, proteins, and growth factors, the therapeutic effect of secretome is hidden in non-coding RNAs such as miR-21, miR-24, and miR-26 carried via exosomes secreted by adequate cells. The whole secretome, including ASC-derived exosomes (ASC-exos) has been proven in many studies to have immunomodulatory, proangiogenic, neurotrophic, and epithelization activity and can potentially be used for neurodegenerative, cardiovascular, respiratory, inflammatory, and autoimmune diseases as well as wound healing treatment. Due to limitations in the use of stem cells in cell-based therapy, its secretome with emphasis on exosomes seems to be a reasonable and safer alternative with increased effectiveness and fewer side effects. Moreover, the great advantage of cell-free therapy is the possibility of biobanking the ASCs secretome. In this review, we focus on the current state of knowledge on the use of the ASCs secretome in stem cell-free therapy.

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The application of stem cell therapy and brown adipose tissue transplantation in metabolic disorders

Cited by 14 publications

References 73 publications

Adipose‐derived stromal cells for nonhealing wounds: Emerging opportunities and challenges

Adipose‐derived stromal cells for nonhealing wounds: Emerging opportunities and challenges

Skeletal muscle provides a pro‐browning microenvironment for transplanted brown adipose tissue to maintain its effect to ameliorate obesity in ob/ob mice

Adipose-Derived Stem Cells Secretome and Its Potential Application in “Stem Cell-Free Therapy”

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