Safety of Adipose-Derived Mesenchymal Stem Cells (MSCs)
With all novel and progressive treatments, the medical industry is understandably concerned about safety. At Surecell, our patients’ safety is our number one priority. Studies have shown that even at high doses, treatment with adipose derived MSCs caused no serious side effects. In addition, no immune-rejection responses or tumour developments have been observed (1).
In fact, adipose derived mesenchymal stem cells satisfy all the ideal criteria for a regenerative medical application (2):
- They can be found in abundant quantities (millions to billions)
- They can be harvested by a minimally invasive procedure
- They can differentiate along multiple cell lineage pathways in a regulated and reproducible manner
- They can be safely and easily administrated to a patient
- They can be manufactured in a safe and regulated way
An optimal vascular supply is crucial to tissue healing. Studies have found that administration of MSCs stimulates formation of vessel-like structures and can improve vessel wall (endothelial) function. This can assist with healing from coronary events (such as heart attacks), pulmonary hypertension, primary and post-surgical skin wounds, and cosmetic fat grafting (3).
Stroke is a devastating incident, which can leave many patients with functional and cognitive impairment. A number of studies have shown that administration of MSCs can enhance recovery and improve outcomes for patients. They found that administration of adipose derived MSCs to affected animals resulted in the release of multiple regenerative growth factors, such as brain-derived neurotrophic factor (BDNF)(4), insulin-like growth factor-1 (IGF-1)(5) and vascular endothelial growth factor (VEGF)(6). From this we may infer that treatment with MSCs encourages repair and regrowth of nerves, as well as surrounding brain matter.
It has also been observed that adipose derived stem cells had a higher proliferative activity and differentiation than bone marrow derived stem cells. Also considering their significantly better safety profile, this indicates that adipose tissue is a preferable source for cell therapy (6). There are currently clinical trials taking place to further assess the safety and efficacy of MCSs in stroke patients.
Alzheimer’s dementia is a recalcitrant disease causing cognitive decline that can be very upsetting, both to patients and to their families. Treatment options are limited, however intravenous administration of adipose-derived MSCs to mice significantly improved their memory. The study found that intravenously administered MSCs actually crossed the blood brain barrier, increasing levels of IL- 10 and VEGF in the brain. These results indicate that MSCs could be used both in the prevention and in the treatment of Alzheimer’s disease (7).
Type 1 Diabetes Mellitus
Type 1 Diabetes (T1DM) is a notoriously challenging disease, which requires life long medical care and intervention. There is currently no definitive cure, and many patients suffer long-term complications. The regenerative capability of MSCs can potentially be harnessed to replace the pancreatic cells of diabetic patients (8).
The long-term effects of MSC therapy have been studied in streptozocin-induced diabetic mice. Transient reduction in glucose levels following administration of MSCs has been well documented. Further recent study has found that multiple intravenous MSC injections, 2 weeks apart, have the ability to increase insulin production and stabilize glucose levels. In fact, after 6 months, the authors found that MSC cells had been engrafted into the liver tissue, and were producing their own insulin (9). This shows exciting prospects for the long-term therapy of T1DM.
Type 2 Diabetes Mellitus (T2DM)
A similar experiment used a combination of streptozocin and a high-fat diet to induce type 2 diabetes in rats. This study found that by infusing MSCs, not only did insulin production increase, but also insulin resistance was ameliorated (10). The latter is a key characteristic of T2DM. This indicates that intravenous administration of MSCs can be beneficial in maintaining glucose balance in both T1DM and T2DM.
Chronic Kidney Disease
Many disease processes can ultimately result in chronic kidney failure. A recent study found that adipose-derived stem cells, administered as a single intravenous infusion, resulted in a significant improvement in kidney function. Multiple regenerative biomarkers were detected and these directly corresponded with the improvement (11). This paper suggests that MSCs offer a minimally invasive, low-risk method of slowing disease progression.
- Ra JC, Shin IS, Kim SH, Kang SK, Kang BC, Lee HY, et al. Safety of intravenous infusion of human adipose tissue-derived mesenchymal stem cells in animals and humans. Stem cells and development. 2011 Aug;20(8):1297-308. PubMed PMID: 21303266.
- Gimble JM, Katz AJ, Bunnell BA. Adipose-derived stem cells for regenerative medicine. Circulation research. 2007 May 11;100(9):1249-60. PubMed PMID: 17495232.
- Zuk P. Adipose-derived stem cells in tissue regeneration: a review. ISRN Stem Cells. 2013.
- Chung JY, Kim W, Im W, Yoo DY, Choi JH, Hwang IK, et al. Neuroprotective effects of adiposederived stem cells against ischemic neuronal damage in the rabbit spinal cord. Journal of the neurological sciences. 2012 Jun 15;317(1-2):40-6. PubMed PMID: 22475376.
- Wei X, Zhao L, Zhong J, Gu H, Feng D, Johnstone BH, et al. Adipose stromal cells-secreted neuroprotective media against neuronal apoptosis. Neuroscience letters. 2009 Oct 2;462(1):76-9. PubMed PMID: 19549558.
- Ikegame Y, Yamashita K, Hayashi S, Mizuno H, Tawada M, You F, et al. Comparison of mesenchymal stem cells from adipose tissue and bone marrow for ischemic stroke therapy. Cytotherapy. 2011 Jul;13(6):675-85. PubMed PMID: 21231804.
- Kim S, Chang KA, Kim J, Park HG, Ra JC, Kim HS, et al. The preventive and therapeutic effects of intravenous human adipose-derived stem cells in Alzheimer's disease mice. PloS one. 2012;7(9):e45757. PubMed PMID: 23049854. Pubmed Central PMCID: 3458942.
- Mabed M, Shahin M. Mesenchymal stem cell-based therapy for the treatment of type 1 diabetes mellitus. Current stem cell research & therapy. 2012 May;7(3):179-90. PubMed PMID: 22023626.
- Ho JH, Tseng TC, Ma WH, Ong WK, Chen YF, Chen MH, et al. Multiple intravenous transplantations of mesenchymal stem cells effectively restore long-term blood glucose homeostasis by hepatic engraftment and beta-cell differentiation in streptozocin-induced diabetic mice. Cell transplantation. 2012;21(5):997-1009. PubMed PMID: 22004871.
- Si Y, Zhao Y, Hao H, Liu J, Guo Y, Mu Y, et al. Infusion of mesenchymal stem cells ameliorates hyperglycemia in type 2 diabetic rats: identification of a novel role in improving insulin sensitivity. Diabetes. 2012 Jun;61(6):1616-25. PubMed PMID: 22618776. Pubmed Central PMCID: 3357293. 11. Villanueva S, Carreno JE, Salazar L, Vergara C, Strodthoff R, Fajre F, et al. Human mesenchymal stem cells derived from adipose tissue reduce functional and tissue damage in a rat model of chronic renal failure. Clinical science. 2013 Aug;125(4):199-210. PubMed PMID: 23480877.