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WJ-MSCs Mitochondrial Transfer: A Newly Emerging Regenerative Therapy

Kristiane Polido

The Wharton’s jelly-derived mesenchymal stem cells (WJMSCs) are known in clinical and basic science research for having unique properties such as fewer ethical issues than other kinds of stem cells, little to no tumorigenicity, and immune responses that are much milder than other stem cell sources. More so, the WJ-MSCs are the only type of stem cell to date with both immunomodulatory and regenerative functions. Recently, there has been an increasing body of research regarding the use of WJ-MSCs to recover from cell injury and tissue degeneration caused by mitochondrial damage. As such,
WJ-MSC mitochondrial transfer becomes a pharmaceutical target for tissue repair and potential therapy for asthma, stroke, and myocardial infarction.

Studies in recent years show the efficacy of other sources of mesenchymal stem cells such as the adipose, dental pulp, and Wharton’s jelly in ameliorating damage to tissues. Although the extent of the capacity of these tissues is relatively unexplored, studies are showing that they, like the bone marrow-derived mesenchymal stem cells, also have the potential for regenerative therapy.

Recapturing lost mitochondrial function
One of the first studies to use WJ-MSCs as mitochondrial donors identified the novel role of WJMSCs in transferring mitochondria to cells with dysfunctional mitochondria. The resulting combination revealed that the recipient cells have replenished mtDNA, expression of mtDNA-encoded proteins, normalized respiratory function, boosted cellular bioenergetics, and OXPHOS-dependent cellular growth and motility. Moreover, the results also demonstrated that mitochondria-related functions remained active after at least 45 passages in 139 days, suggesting that the method used can sustain
the therapeutic effect of mitochondrial transfer from WJ-MSCs.

Reduction of oxidative stress and improving mitochondrial bioenergetics
A more recent study in 2017 reported that mitochondrial transfer from WJ-MSC to myoclonus epilepsy associated with ragged-red fibers (MERRF) cybrid cells results in partial reduction of mtDNA mutation load, oxidative stress, and mitochondrial bioenergetics. More so, they also showed a marked improvement in mitochondria-dependent viability, the balance of mitochondrial dynamics, and resistance against apoptotic stress.

Mitochondrial transfer, coupled with mtDNA transfer, partly reduced the mutation load on the MERFF cells. The reduced mutation load contributes to the enhancement of the translation of mtDNA-encoded proteins. The corrected mitochondrial translation assists the respiratory enzyme complex to perform mitochondrial bioenergetics, such as facilitating electron transport, generating mitochondrial membrane potential, oxygen consumption, and ATP production through oxidative phosphorylation.

Research on mitochondrial transfer from mesenchymal stem cells is associated with the reinstating of aerobic restoration and mitochondrial function in the recipient cells. Most of the studies done on the mitochondrial
transfer using mesenchymal stem cells use cells derived from the bone marrow. Some newly-emerging research shows that the source of the stem cell will significantly determine its mitochondrial donor property. More so, this correlates with the tissue rescue and intrinsic respiratory state. This emphasizes the importance of choosing the optimum tissue source for the regeneration of damaged tissues.

The WJ-MSC is considered as the more ethical choice for MSC treatments because it is accessed through the human umbilical cord (hUC), and the cells are harvested painlessly from millions of births worldwide, without any fear for donor site morbidity. More so, WJ-MSCs are easy to isolate and to culture, with its high proliferation rate and the notable ability to retain its stem cell properties, for many passages in vitro. Compared to adult MSCs, WJ-MSCs are known to be hypoimmunogenic, non-tumorigenic, multipotent, and are less heterogenous, making it more ideal for novel therapies.

The studies on Wharton’s Jelly-MSC provide a solid foundation for its use in mitochondrial transfer in regenerative therapy. The reported WJ-MSC ability to rescue cells with defective mitochondrial function through donating healthy mitochondria may lead to new insights into the development of more efficient strategies to treat diseases related to mitochondrial dysfunction. Nevertheless, the efficiency and therapeutic effects if WJMSCs in transferring mitochondria to damaged cells due to mitochondrial diseases need further investigation.

Reference (Dec-20-A1)

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