Abstract：
:After spinal cord injury (SCI), loss of cells and damage to ascending and descending tracts can result in paralysis. Current treatments for SCI are based on patient stabilization, and much-needed regenerative therapies are still under development. To activate and instruct stem and progenitor cells or injured tissue to aid SCI repair, it is important to modify the injury environment for a protracted period, to allow time for cell activation, proliferation and appropriate fate differentiation. Shh plays a critical role in spinal cord formation, being involved in multiple processes: it promotes production of motor neurons and oligodendrocytes from ventral cord progenitor cells and serves as an axon guidance molecule. Hence Shh is a candidate pleiotropic beneficial environmental factor for spinal cord regeneration. Here we show that administration of biodegradable microspheres that provide sustained, controlled delivery of Shh resulted in significant functional improvement in two different mouse models of SCI: contusion and dorsal hemioversection. The mechanism is multifactorial, involving increased proliferation of endogenous NG2+ oligodendrocyte lineage cells, decreased astrocytic scar formation and increased sprouting and growth of corticospinal (CST) and raphespinal tract (RST) fibers. Thus, long-term administration of Shh is a potential valuable therapeutic intervention for SCI.
journal_name
Biomaterialsjournal_title
Biomaterialsauthors
Lowry N,Goderie SK,Lederman P,Charniga C,Gooch MR,Gracey KD,Banerjee A,Punyani S,Silver J,Kane RS,Stern JH,Temple Sdoi
10.1016/j.biomaterials.2011.12.048subject
Has Abstractpub_date
2012-04-01 00:00:00pages
2892-901issue
10eissn
0142-9612issn
1878-5905pii
S0142-9612(11)01531-6journal_volume
33pub_type
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