So far, however, there is no indication that unknown toxicity occurs in autoimmune disease patients. The considerable toxicity of HSCT in general is the reason that the treatment should only be performed in experienced transplant units. When selecting a patient for such a treatment, one should ask the following questions:
Explore This IssueNovember 2008
- Is the disease potentially more dangerous than the treatment? (Current estimates are around 5% transplant-related mortality.)
- Is the patient in too advanced a state of vital organ damage such that the chances of meaningful benefit are outweighed by the higher risk of transplant-related mortality (e.g., advanced lung fibrosis with diffusing capacity of the lung for carbon monoxide of less than 30% predicted)?
- Does the patient and his or her family understand that the stem-cell transplant is only to “rescue the normal blood cells” after heavy immunoablation and not to supply some special healing action on the diseased organs?
- Have you exhausted the existing conventional proven treatments for this autoimmune disease?
If the answers to these questions are affirmative, then it is reasonable to enter such a patient into one of the experimental trials. Only through prospective randomized trials are hematologists able to offer long-term cure to certain leukemia patients, even though the exact cause of leukemia remains unknown.
Although anecdotes have a limited place in clinical research, the experience of seeing a young scleroderma patient go from an exhausted and hidebound patient to a near normal individual over three to six months has inspired many of the investigators to push on with the prospective trials to reach the correct conclusion. We owe this to those patients who have put their trust in the program already, not all of whom have done well.
Multipotent MSC for Autoimmune Diseases
Mesenchymal stromal cells (MSCs) are also referred to as mesenchymal stem cells, though their true “stemness” has yet to demonstrated.11 MSCs are capable of differentiating in vitro and in vivo to different MSC lineages, including adipose, bone, cartilage, muscle, and myelosupportive stroma. MSCs may be isolated from bone marrow, skeletal muscle, adipose tissue, synovial membranes, and other connective tissues of human adults, as well as cord blood and placental products, and are defined by using a combination of phenotypic markers and functional properties.
In vitro, MSCs have vast proliferative potential, can clonally regenerate, and can give rise to differentiated progeny. These cells also exhibit anti-proliferative and anti-inflammatory properties in vitro and in vivo, making them candidates for treatment of acute inflammatory autoimmune disease.12 Regardless of whether or not MSCs are true stem cells, clinical benefit from MSCs may not require sustained engraftment of large numbers of cells or differentiation into specific tissues. It is possible that a therapeutic benefit can be obtained by local paracrine production of growth factors and a provision of temporary antiproliferative and immunomodulatory properties.