An Indian team from Delhi, India has identified a protein that increases the transfer of mitochondria from mesenchymal stem cells to lung cells, thus augmenting the healing of lung cells.
Stem cells like mesenchymal stem cells from bone marrow, fat, tendons, liver, skeletal muscle, and so on secrete a host of healing molecules, but they also form bridges to other cells and export their own mitochondria to heal damaged cells. Mitochondria are the structures inside cells that make energy. Damaged cells can have serious energy deficiencies and mitochondrial transfer ameliorates such problems (see Cárdenes N et al, Respiration. 2013;85(4):267-78).
This present work from the laboratory of Anurag Agrawal, who is housed in the Centre of Excellence in Asthma & Lung Disease, at the CSIR‐Institute of Genomics and Integrative Biology in Delhi, India has identified a protein called Miro1 that regulates the transfer of mitochondria to recipient cells.
Mitochondrial transfer has so many distinct benefits that stem cell scientists hope to engineer stem cells to transfer more of their mitochondria to damaged cells, and Miro1 might be a target for such stem cell engineering experiments.
Mitochondrial transfer between stem cells and other cells occurs by means of tunneling nanotubes, which are thread-like structures formed from the plasma membranes of cells that form bridges between different cell types. Under stressful conditions, the number of these nanotubes increases.
In the present study. stem cells engineered to express more Miro1 protein transferred mitochondria more efficiently than control stem cells. When used in mice with damaged lungs and airways, these Miro1-overexpressing cells were therapeutically more effective than control cells.
The hope is to use Miro1 manipulations to make better stem cell therapies for human diseases.
To summarize this work:
1. MSCs donate mitochondria to stressed epithelial cells (EC) that have malfunctioning mitochondrial. Cytoplasmic nanotubular bridges form between the cells and Miro‐1 mediated mitochondrial transfer occurs unidirectionally from MSCs to ECs.
2. Other mesenchymal cells like smooth muscle cells and fibroblasts express Miro1 and can also donate mitochondria to ECs, but with low efficiency. ECs have very low levels of Miro1 and, as a rule, do not donate mitochondria.
3. Enhanced expression of Miro1 in mesenchymal cells increases their mitochondrial donor efficiency. Conversely, cells lacking Miro1 do not show MSC mediated mitochondrial donation.
4. Miro1‐overexpressing MSCs have enhanced therapeutic effects in three different models of allergic lung inflammation and rat poison-induced lung injury. Conversely, Miro1‐depleted MSCs lose much of their therapeutic effect. Miro1 overexpression in MSCs may lead to more effective stem cell therapy.