Bone Marrow Stem Cells Rejuvenate Tissue Mitochondria

Within almost every cell in your body are small vesicles called mitochondria that act as the powerhouses of the cell. Chemical energy is synthesized in the mitochondria, and without these vital structures, the ability of the cell to do all the incredible things that it does goes away. Cells are chemical and biological marvels but all the things they do require energy.

Cells make their energy from energy-rich food molecules such as sugars, amino acids, and fats. Cells degrade these energy-rich food molecules to smaller molecules, and harvest the released energy in the form of high-energy electrons and am energy storage molecule called “ATP.”  ATP stands for “adenosine triphosphate,” and this molecule as a series of high-energy phosphate anhydride bonds that store energy. The high-energy electrons are carried by electron carriers and these carriers give their high-energy electrons to electron transport chains that are embedded in the membranes of mitochondria and the electrons are passed through the electron transport chains, ultimately to molecular oxygen, which makes water. Passing the electrons down the electron transport chain to make water releases a whole lot of energy that is captured and stored in the form of ATP. Thus mitochondria are the “powerhouses” of the cell.

Mitochondria, however, pay a price for their assiduous energy making. All their exposure to oxygen (a toxic molecule under various conditions) and versions of oxygen with extra electrons (known as reactive oxygen species or ROS) tends to damage the mitochondria over time. With time, the mitochondria become to damaged that they are unable to make energy for the cell. Cells that cannot make energy are of no value to the body. How do you fix what has been broken?

Cells have ways to destroy damaged mitochondria (autophagy) and working mitochondria also have the capacity to divide. However, what if the mitochondria become collectively so damaged that the cell cannot make its own energy?

New work shows that stem cells can come to the rescue. A paper in the journal Nature Medicine (18(5)) by Mohammad Naimul Islam and colleagues from the laboratory of Jahar Bhattacharya at the College of Physicians and Surgeons of Columbia University, New York, has discovered something potentially ground breaking. The paper, entitled “Mitochondrial transfer from bone-marrow–derived stromal cells to pulmonary alveoli protects against acute lung injury” used a mouse model to study lung damage. They sprayed a molecule from bacteria into the respiratory systems of mice. This molecule, lipopolysaccharide (LPS) is found in the outer-most membrane of certain types of bacteria, and production of this molecule and its distribution throughout the body causes tissue damage and inflammation. After spraying LPS into the lungs, they added bone marrow-derived stem cells from mouse or human bone marrow to help mitigate the damage induced by exposure to LPS.

They used live optical studies to examine the nature of the interaction of bone marrow MSCs with respiratory cells. Optical viewing of the respiratory tract showed that intimate connections were made between the stem cells and the respiratory cells. These connections consisted of special channels that are normally found between cells that are in the process of transferring materials between each other.

The astounding result was that the connections between the stem cells and respiratory cells showed the transfer of mitochondria from the stem cells to the respiratory cells. The transfer of mitochondria resulted in increased concentrations of ATP in respiratory cells and also decreased the signs and symptoms of inflammation within the respiratory tract. Mutant stem cells that had defective mitochondria were not able to abrogate the damage to the respiratory system.

This is a significant finding, since as well as being the powerhouse of the cell, mitochondria also control the onset of programmed cell death. Fresh, new mitochondria probably rejuvenate the cell by preventing the onset of programmed cell death, and refurbishing the energy-production machinery of the cell. This significant finding elucidates what might be a major mechanism of how stem cells heal damaged tissue.

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Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).

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