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Stem Cell Therapy & Iron - Be Careful

I came across an excellent and interesting paper [1] related to Stem Cell therapy and how iron status can effect the response to Stem Cell therapy. I have know several folks who have had different responses, and one client in particular who had high intracellular iron and high unbound iron had a very adverse reaction to Stem Cell Therapy - consistent with the thesis in this paper.


For those of you who use Stem Therapy, or are considering Stem Cell Therapy - please consider reading this article and the implications related to iron status. In particular note hepcidin, ferritin, and haem oxygenase-1 (HMOX1) in the below extract of the paper.


"Mesenchymal stem cells (MSCs) are located in various tissues where these cells show niche‐dependent multilineage differentiation and secrete immunomodulatory molecules to support numerous physiological processes. Due to their regenerative and reparative properties, MSCs are extremely valuable for cell‐based therapy in tackling several pathological conditions including COVID‐19. Iron is essential for MSC processes but iron‐loading, which is common in several chronic conditions, hinders normal MSC functionality. This not only aggravates disease pathology but can also affect allogeneic and autologous MSC therapy. "[1]


"MSCs demonstrate reparative and regenerative properties in vivo and are extremely valuable for cell‐based therapy. Iron and iron‐related proteins play an essential role in MSC physiology. The latter include hepcidin, ferroportin, transferrin receptor, lactoferrin, lipocalin‐2, BMPs and HIFs. Excess iron causes detrimental effects on the MSCs and alter their functionality, differentiation potential, haematopoiesis supportive functions, epigenetics and the signalling pathways of ROS, PI3K/AKT, MAPK, p53, AMPK/MFF/DRP1 and Wnt. Endogenous proteins like hepcidin, ferritin and haem oxygenase‐1 can protect the MSCs from iron‐loading or its effects. In addition, exogenous iron chelators like deferasirox and deferoxamine, herbs like Herba Epimedii and A. membranaceus, and naturally occurring compounds like melatonin and α‐lipoic acid can reduce or reverse some of the detrimental effects of iron‐loading on the MSCs. MSCs contribute to the disease pathology of iron‐loading conditions like hereditary hemochromatosis, diabetes, β‐thalassaemia and MDS. The review summarizes the iron‐mediated processes in the MSCs and helps understand MSC contribution to physiology and pathology under normal and iron‐loaded conditions, respectively. This knowledge can help identify signaling pathways, molecular targets and endogenous/exogenous compounds that could be explored to formulate adjunctive iron‐based therapy to ameliorate numerous conditions of iron excess. Also, it can inform MSC therapeutics, as it recognises the challenges of autologous MSC therapy in iron‐loaded conditions" [1]


[1] Role of iron and iron‐related proteins in mesenchymal stem cells: Cellular and clinical aspects. Kosha Mehta. Cellular Physiology, Received: 26 November 2020 | Revised: 17 March 2021 | Accepted: 19 March 2021 DOI: 10.1002/jcp.30383. J Cell Physiol. 2021;236:7266–7289

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