São Paulo, Brazil -
Bone marrow is classically known to be the site of hematopoiesis, thus "bone marrow transplant" has been successfully used for decades as a means of treating various hematological malignancies in which the recipient hematopoietic compartment is replaced by donor-derived stem cells. More recent investigations have demonstrated that several progenitor cells exist within bone marrow that are capable of differentiating into other tissues, for example cardiac tissue. In fact, clinical trials have been conducted demonstrating beneficial effects of bone marrow infusion in cardiac patients. It is believed that injured tissue, whether neural tissue after a stroke, or injured cardiac tissue, has the ability to selectively attract bone marrow stem cells, perhaps to induce regeneration. While numerous studies have demonstrated bone marrow having therapeutic effect in conditions ranging from liver failure, to peripheral artery disease, the possibility of using bone marrow stem cells in kidney failure has been relatively understudied.
A recent paper (Alexandre et al. Lineage-Negative Bone Marrow Cells Protect against Chronic Renal Failure. Stem Cells 2008 Dec 18) addressed this question.
Researchers used a rat model of chronic renal failure in which one kidney is excised so as to increase the load of the remaining kidney, thus causing a chronic deterioration that resembles the clinical situation of renal failure.
The rats were divided into 4 groups.
Group 1 were sham operated and both kidneys left in place.
Group 2 had a kidney removed but were not administered cells.
Group 3 were administered 2 million lineage negative bone marrow cells on day 15 after one of the kidneys was removed.
Group 4 were administered 2 million lineage negative bone marrow cells on days 15, 30, and 45 after one of the kidneys was removed.
- Expression of inflammatory cytokines was reduced on day 16 in the kidneys of rats recieving stem cells as compared to rats that were nephrectomized but did not recieve cells.
- On day 60 rats recieving stem cells had decreased proteinuria, glomerulosclerosis, anemia, renal infiltration of immune cells and protein expression of monocyte chemoattractant protein-1, as well as decreased interstitial area.
- Injured rats had higher numbers of proliferating cells in the kidney, whereas rats recieving stem cells had less.
- Protein expression of the cyclin-dependent kinase inhibitor p21 and of vascular endothelial growth factor increased after nephrectomy and decreased after Lin(-) cell treatment.
- On day 120, renal function (inulin clearance) was improved in the rats which were administered bone marrow cells compared to controls.
This study supports the possibility of using bone marrow cells for various aspects of kidney failure. Other studies have demontrated that administered stem cells promote kidney repair by secretion of IGF-1, it would be interesting to see if the lineage negative cells used in this study make more of this cytokine.