In 2010, as is typical in a new area of research, a group of scientists performed an animal study to test the potential safety and effectiveness of adipose-derived (from fat) stem and regenerative cells (ADRCs) to treat acute kidney disease.

The results were surprisingly positive, demonstrating that ADRC therapy drastically reduced mortality with 100% of the treated mice surviving as compared to 57% that received the placebo (controls). Likewise, the treated mice had significantly reduced serum creatinine levels vs. the controls.^[1]  Since that study, a series of other studies of acute and chronic kidney disease in small and large animals as well as humans have shown that adult stem cells and other regenerative cells from adipose tissue can potentially help to prevent disease progression, lower serum creatinine levels, reverse fibrous scar (fibrosis) and improve blood flow.^{[2] [3] [4]} Human studies have also shown improved kidney function after stem cell treatment.^[5]

Adipose-Derived Stem and Regenerative Cells (ADRCs)

Body fat, medically known as adipose tissue, is an attractive source of stem and regenerative cells due to its accessibility, abundance and potency compared to other tissue sources such as bone marrow, umbilical cord and placenta. ADRCs can be harvested, processed and re-injected at the bedside in a same-day procedure, and through multiple biologic activities, have been used to improve symptoms, function and quality of life in a wide range of conditions, including acute and chronic kidney disease.^{[6] [7]}

Spirale di degenerazione

Chronic degenerative conditions, including renal failure, follow a similar pattern in their disease process.

Trauma, infection, environmental toxins, unhealthy lifestyle choices (e.g. smoking), hereditary factors or a combination of these negative factors can trigger an inflammatory response. This type of inflammation (acute) is essential for repairing the body, and is usually short-lived, disappearing once the healing process has taken place.

There is another type of lingering inflammatory response which becomes chronic, and affects the entire body, becoming systemic.^[8] Systemic inflammation is a common factor in diseases of aging—this covers a broad spectrum of severe, debilitating and, sometimes, life-threatening conditions, again including renal failure.^{[9] [10]}

In the case of degenerative diseases, the chronic inflammation begins a vicious degenerative process. It recruits the immune system, which is there to fight infections and other disease processes, and to assist healing. The cells in the immune system (immune cells) are there to guard the body. When they sense the enemy, they send out troops of pro-inflammatory molecules called “cytokines” to fight them off.  When this process goes out of control, it is called an inflammatory-immune response. This response is tantamount to having a backseat driver who is chronically overreacting while “helping” you drive your car. The immune response then leads to reduced blood flow (ischemia). Without good circulation, cells die off, scars and fibrosis form, tissues and organs degenerate. We call this the Spiral of Degeneration as use it as a framework for understanding some of the key factors of renal disease.

Loss of kidney function corresponds with inflammation affecting the renal (kidney) filtering system and their small blood vessels. Chronic kidney disease is well known to be associated with diabetes and uncontrolled high blood pressure, gradually worsening renal function over time. The early stages are usually without symptoms. Acute kidney disease can be rapidly provoked by an insufficient fluid status (from a variety of conditions) and from some medications.

Processo di riparazione

Attraverso un meccanismo di comunicazione tra cellule noto come effetto paracrino, le ADRC mobilitano le cellule vicine a lavorare in modo più efficiente. Reclutano i vigili del fuoco, i soccorritori e i riparatori biologici del sito - le cellule staminali residenti - perché tornino al lavoro e facciano la loro parte.

Reclutando altri "riparatori" nel sito (cellule staminali residenti) per rimettersi al lavoro e fare la loro parte, le ADRC riuniscono una squadra allargata e lavorano innanzitutto per ridurre l'infiammazione e le risposte immunitarie iperattive. Una volta che la guida in retrovia diminuisce, continuano il loro lavoro aumentando la circolazione con la crescita di nuovi vasi sanguigni, prevenendo l'ulteriore morte cellulare, affrontando il tessuto cicatriziale e rigenerando i tessuti sani e i nervi. Questo è il modo in cui il corpo guarisce naturalmente, ma se l'insulto di una condizione acuta o cronica è troppo grande, ha bisogno di aiuto.

We call this the Process of Repair.  It involves the multiple mechanisms of action that are needed to bring the systemic inflammation and immune response back to balance.

AMBROSE Cell Therapy for Kidney Disease

Because the primary factors in the Spiral discussed above are found to be involved with renal failure and the multiple repair mechanisms of the ADRCs have been shown to reverse those effects in this condition as well as a range of other serious conditions, patients with kidney disease can potentially benefit from AMBROSE Cell Therapy.

Animal studies have shown that stem cells reduce acute kidney injury by activating specialized white blood cells that initiate healing and kidney tissue repair, and protect against premature cell aging.^{[11] [12] [13]}

Likewise, stem cell treatment of animal chronic kidney disease has been shown to promote recovery of kidney cell energy production^{[14] [15]}, decrease scarring^[16], and decrease inflammation.^[17]

AMBROSE Cell Therapy represents a minimally invasive treatment option for patients with renal disease. Please contact us for more information about treatment, candidacy and how to become a patient.

[1] Z Feng et al Cellule staminali e rigenerative derivate dal tessuto adiposo, fresche e crioconservate, non coltivate, migliorano il danno renale acuto indotto da ischemia-riperfusione, Nefrologia Dialisi Trapianto, Volume 25, Numero 12, 1 dicembre 2010, Pagine 3874-3884

[2] C Donizetti-Oliveira Il trattamento con cellule staminali derivate dal tessuto adiposo previene la progressione della malattia renale Cell Transplantation, Vol. 21, pp. 1727-1741, 2012

[3] A Eirin et al Le cellule staminali mesenchimali derivate dal tessuto adiposo migliorano i risultati della rivascolarizzazione per ripristinare la funzione renale nella stenosi aterosclerotica dell'arteria renale dei suini Stem Cells. 2012 maggio; 30(5): 1030-1041

[4] JJ Rivera-Valdés et al. (2017) Human adipose derived stem cells regress fibrosis in a chronic renal fibrotic model induced by adenine. PLoS ONE 12(12)

[5] El‐Ansary M, Saadi G, Abd El‐Hamid SM. Mesenchymal stem cells are a rescue approach for recovery of deteriorating kidney function. Nephrology 2012;17:650–657.

[6] Guo et al Frazione vascolare stromale: Una realtà rigenerativa? Parte 2: concetti attuali e revisione della letteratura Journal of Plastic, Reconstructive & Aesthetic Surgery (2016) 69, 180e188

[7] JK Fraser PhD e S Kesten MD Cellule rigenerative di derivazione adiposa autologhe: Una piattaforma per applicazioni terapeutiche Advanced Wound Healing Surgical Technology International XXIX

[8] S. Amor L'infiammazione nelle malattie neurodegenerative Immunologia, 129, 154-169

[9] C. Franceschi e J. Campisi L'infiammazione cronica (Inflammaging) e il suo potenziale contributo alle malattie associate all'età J Gerontol A Biol Sci Med Sci 2014 June;69(S1): S4-S9

[10] Suliman ME, Stenvinkel P. Contributo dell'infiammazione alla malattia vascolare nei pazienti con malattia renale cronica. Saudi J Kidney Dis Transpl 2008;19:329-45

[11] Geng, Y.; Zhang, L.; Fu, B.; Zhang, J.; Hong, Q.; Hu, J.; Li, D.; Luo, C.; Cui, S.; Zhu, F.; et al. Mesenchymal stem cells ameliorate rhabdomyolysis-induced acute kidney injury via the activation of m2 macrophages. Stem Cell Res. Ther. 2014, 5, 80

[12] Lee, S.J.; Ryu, M.O.; Seo, M.S.; Park, S.B.; Ahn, J.O.; Han, S.M.; Kang, K.S.; Bhang, D.H.; Youn, H.Y. Mesenchymal stem cells contribute to improvement of renal function in a canine kidney injury model. In Vivo 2017, 31, 1115–1124

[13] Rodrigues, C.E.; Capcha, J.M.; de Braganca, A.C.; Sanches, T.R.; Gouveia, P.Q.; de Oliveira, P.A.; Malheiros, D.M.; Volpini, R.A.; Santinho, M.A.; Santana, B.A.; et al. Human umbilical cord-derived mesenchymal stromal cells protect against premature renal senescence resulting from oxidative stress in rats with acute kidney injury. Stem Cell Res. Ther. 2017, 8, 19

[14] Yoon, Y.M.; Han, Y.S.; Yun, C.W.; Lee, J.H.; Kim, R.; Lee, S.H. Pioglitazone protects mesenchymal stem cells against p-cresol-induced mitochondrial dysfunction via up-regulation of pink-1. Int. J. Mol. Sci. 2018, 19, 2898

[15] Lira, R.; Oliveira, M.; Martins, M.; Silva, C.; Carvalho, S.; Stumbo, A.C.; Cortez, E.; Verdoorn, K.; Einicker-Lamas, M.; Thole, A.; et al. Transplantation of bone marrow-derived mscs improves renal function and na(+)+k(+)-atpase activity in rats with renovascular hypertension. Cell Tissue Res. 2017, 369, 287–301

[16] Wu, H.J.; Yiu, W.H.; Li, R.X.; Wong, D.W.; Leung, J.C.; Chan, L.Y.; Zhang, Y.; Lian, Q.; Lin, M.; Tse, H.F.; et al. Mesenchymal stem cells modulate albumin-induced renal tubular inflammation and fibrosis. PLoS ONE 2014, 9, e90883

[17] Abdel Aziz, M.T.; Wassef, M.A.; Ahmed, H.H.; Rashed, L.; Mahfouz, S.; Aly, M.I.; Hussein, R.E.; Abdelaziz, M. The role of bone marrow derived-mesenchymal stem cells in attenuation of kidney function in rats with diabetic nephropathy. Diabetol. Metab. Syndr. 2014, 6, 34