Growth factors and stem cells as treatments for stroke recovery.
Both polypeptide growth factors and stem cell populations from bone marrow and umbilical cord blood hold promise as treatments to enhance neurologic recovery after stroke. Growth factors may exert their effects through stimulation of neural sprouting and enhancement of endogenous progenitor cell proliferation, migration, and differentiation in brain. Exogenous stem cells may exert their effects by acting as miniature "factories" for trophic substances in the poststroke brain. The combination of growth factors and stem cells may be more effective than either treatment alone. Stroke recovery represents a new and relatively untested target for stroke therapeutics. Whereas acute stroke treatments focus on agents that dissolve blot clots (thrombolytics) and antagonize cell death (neuroprotective agents), stroke recovery treatments are likely to enhance structural and functional reorganization (plasticity) of the damaged brain. Successful clinical trials of stroke recovery-promoting agents are likely to be quite different from trials testing acute stroke therapies. In particular, the time window of effective treatment to enhance stroke recovery is likely to be far longer than that for acute stroke treatments, perhaps days or weeks rather than minutes or hours after stroke. This longer time window means that time is available for careful screening and testing of potential subjects for stroke recovery trials, both in terms of size and location of cerebral infarcts and in type and severity of neurologic deficits. Detailed baseline information can be obtained for each patient against which eventual clinical outcome can be compared. Finally, separate and detailed outcome measures can be obtained in both the sensorimotor and cognitive neurologic spheres, because it is possible that these two kinds of function may recover differently or be differentially responsive to recovery-promoting treatments. Stroke recovery represents an important and underexplored opportunity for the development of new stroke treatments.
Cairns
Kevin
K
Department of Physical Medicine and Rehabilitation, Harvard Medical School, 125 Nashua Street, Boston, Massachusetts 02114, USA.
Finklestein
Seth P
SP
D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D016222:Fibroblast Growth Factor 2 / Q000627:therapeutic use*; D019922:GAP-43 Protein / Q000627:therapeutic use*; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020127:Recovery of Function; D033581:Stem Cell Transplantation; D020521:Stroke / Q000188:drug therapy* / Q000601:surgery*; D016212:Transforming Growth Factor beta
C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D019922:GAP-43 Protein; D018696:Neuroprotective Agents; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2