Fat : The future of regenerative therapy

Regenerative therapy is a cell-based technique using stem cells to boost tissue regeneration. Though many different stem cells are used, one of the most promising is fat-derived adipose stem cells.

 
When tissue is damaged your body will regenerate it by replacing damaged cells through cell growth and division. Your DNA determines how your body knows when and where to regenerate. Similar to your computer hard drive storing software, your DNA is hardwired to execute complex regenerative steps to heal your body during trauma. However, what happens when our DNA is corrupted or the damage is too great for our body to regenerate?
 

What is regenerative therapy?

Regenerative therapy is the reconstruction or rejuvenation of damaged tissue using stem-cell-based techniques. Stem cells are the cellular “seeds” of our body that allow our organs and tissues to regenerate. Typically, when the cells in our body mature, a significant trade-off is made. Cells lose the ability to divide but they gain a specialized function. Muscle cells, for example, gain the specialization for contracting. If our bodies were completely made of specialized cells, any damage may be life-threatening since these cells cannot regenerate. To solve this, our bodies store a small amount of stem cells that are able to divide and later specialize to replace damaged cells. For example, muscle stem cells divide to repair and grow damaged muscle tissue.
 

Regenerative therapy uses stem cells to boost tissue recovery

Regenerative therapy takes advantage of the utility of stem cells by harvesting them from a donor and reintroducing them to a patient to boost normal tissue recovery. This is especially critical for patients suffering from genetic degenerative diseases, whose stem cells are dysfunctional, and injuries that are too great to repair naturally. By injecting stem cells directly into the affected tissue, these cells will seed the patient with healthy stem cells which can repopulate the affected area with healthy tissue and curb the degenerative process. 
 
Alternatively, harvested stem cells can be grown, which mimics normal tissue elasticity to promote the stem cells to divide, reorganize, and specialize into tissues which can be transplanted to the patients. A common application of this approach is regenerating skin grafts for burn-wound victims to help grow healthy skin during their recovery. Due to these advantages, regenerative therapy is a vital technique that can help treat and potentially cure many genetic diseases and physical ailments. A recent review in the journal Biotechnology Advances by scientists in the Czech Republic summarizes what scientists know so far about the use of stem cells in regenerative therapy.
 

Adult and embryonic stem cells have different potentials

Not all stem cells are the same. Depending on where the stem cell originates, their potential for specialization can be vastly different. Two major types of stem cells are adult and embryonic stem cells.
 
Adult stem cells are found throughout the human body and are typically limited to specialize into only a few or even one type of mature cell. Common adult stem cells that are used in regenerative therapy include fat, bone marrow, skin, and blood. While these stem cells vary in difficulty of harvesting, they can be challenging to use in regenerative therapy because so few can be harvested per patient as well as their difficulty in growing in culture.
 
On the other hand, embryonic stem cells are ideal for regenerative therapy since they are pluripotent, meaning they are capable of becoming different kinds of cells. Pluripotent stem cells are able to specialize into any type of cell within the human body and have a high degree of division.
Pluripotent stem cells grow very well in lab cultures. This allows researchers to grow a large batch of stem cells from a small harvest to be used for many treatments and experiments. They can also be differentiated into any type of cell which allows them to be highly versatile in many different regenerative therapies. Yet, they are not commonly used in regenerative therapy due to their ethical controversy.
 

Ethical issues in embryonic stem cells

Pluripotent stem cells have the potential to become any type of cell in the body because of their origins within the human body. They are collected from a small patch of cells within one-week human embryos called the epiblast, which makes pluripotent stem cells a serious ethical dilemma. However, researchers are experimenting on a similar type of cell without the ethical controversies.
 

Artificial pluripotent stem cells

Similar to normal pluripotent stem cells, induced pluripotent stem cells can differentiate into any cell within the human body. They are artificially made from converting normal adult cells into pluripotent cells through the process of dedifferentiation.
 
Dedifferentiation usually involves collecting a small number of cells from a consenting adult through a mouth swap, blood sample, or tissue sample. The cells are then exposed to a biomedically engineered virus carrying DNA instructions to reprogram the adult cell into an induced pluripotent stem cell. These DNA instructions allow the cell to express key pluripotent genes to be converted into an induced pluripotent stem cell with all the benefits and no ethical controversy.
 
However, this process can be rather expensive and takes a long time to perform and verify for medical treatments. Indeed, a new source of stem cells that are flexible, easy to use, versatile, and efficient is necessary for regenerative therapy.
 

Adipose stem cells

When one thinks of fat, one of the last things they might think of is how many stem cells are in it. But researchers have found that adipose tissue is a plentiful source of adipose stem cells that can be easily harvested and be applied for regenerative therapy. In fact, 500x more stem cells can be harvested from fat than from bone marrow and with minimal harm.
 
Recent research on adipose (fat) stem cells found they have a high replication and growth factor secretion rate making them a viable choice for certain regenerative therapies. When researchers used adipose stem cells to treat spinal cord injuries in rats, they found it secreted more growth factors than bone marrow stem cells. These growth factors are critical for promoting regeneration in damaged tissue which was seen in higher rates of spinal cord injury recovery in adipose stem cell than in bone marrow stem cells.
 
Adipose stem cells were also found to have some success in treating Parry-Romberg syndrome, a hemi-facial degenerative disease, as well as Perineal Crohn’s disease, an inflammatory disease making them highly versatile for a diverse range of diseases.
 

Using stem cells from fat for cosmetic surgery

One of the most popular uses of adipose stem cells is cosmetic surgery. Cell-assisted lipotransfer involves removing small tissues of fat from a patient and regrafting them into other regions for reconstructing features and enhancing aesthetics. This is commonly used for breast enhancement in boosting breast volume and symmetry. Due to the growth factor secretions of adipose stem cells, they are better able to help promote vascularization in the grafted regions to improve fat retention for a more permanent fix. Indeed, cell-assisted lipotransfer is estimated to have a 40-75% success rate, giving women a less synthetic option for breast augmentation.
 
When applied to animal studies, researchers found adipose stem cells may be far more flexible in treating disorders than previously thought. Adipose stem cells were found to have significant beneficial effects in treating pulmonary arterial hypertension, optic nerve damage, and limiting vocal fold fibrosis in rats. Comparatively, these cells improved neovascularization in fat grafts on mice, suggesting they may be used more broadly for any physical trauma.
 
However, the clinical risks of adipose stem cells use are not yet fully explored. Due to their growth factor secretions, researchers suspect they can promote cancer metastasis. Additionally, there is controversial evidence that adipose stem cells may be associated with cardiac diseases. Since these cells were only discovered in 2002, it goes without question that further research is needed in order to fully unveil their safety and clinical use in regenerative therapy.
 

Promising applications for fat-derived stem cells

Regenerative therapy is a cell-based clinical technique which uses stem cells to boost tissue regeneration. Though many different stem cells are used, one of the most promising is fat-derived adipose stem cells. These cells are relatively abundant and easy to collect within the human body. Combined with their ability to secrete key growth factors in vascularization, adipose stem cells are ideal for regenerative therapy in treating certain diseases and relatively successful in cosmetic surgeries. Though there is controversial evidence that they are associated with cardiac diseases and can be linked with cancer progression, adipose stem cell research will continue to uncover their potential for regenerative therapy.
 
References:
(1) Bacakova, L. et al. Stem cells: their source, potency and use in regenerative therapies with focus on adipose-derived stem cells – a review. Biotechnol. Adv. 0–1 (2018). doi:10.1016/J.BIOTECHADV.2018.03.011
(2) Arshad, Z. et al. Cell assisted lipotransfer in breast augmentation and reconstruction: A systematic review of safety, efficacy, use of patient reported outcomes and study quality. Jpras Open10, 5–20 (2016).
(3) Löhle, M. et al. Differentiation efficiency of induced pluripotent stem cells depends on the number of reprogramming factors. Stem Cells30, 570–9 (2012).