A). Regulatory Functions

1) As pericytes in tissues: Release of tissue-specific exosomes and secretion of regulatory molecules

2) Injected as free cells into the intra-articular space to control pain in osteoarthritis: Immunomodulatory effects with release of anti-inflammatory molecules and other regulatory mediators

3) Injected as free cells into the blood steam: Localization and functional impact at sites of renal injury

4) Homing to sites of injury: Localization to tissues such as the heart (myocardial infarction) or brain (stroke): Release mediators to assist endogenous cells to initiate repair and influence inflammation

Current Limitations

1) Understanding of why homing rate to injury/diseased sites so low

2) Knowledge of recognition systems used by MSC to perform regulatory functions

3) Why proliferation and secretory activities decline with age

B). Activities Based on Pluripotency and Proliferation

1) Self-renewal in tissues where localized as pericytes: Needed to maintain tissue integrity

2) In vitro development of tissue-engineered candidates for specific organ repair or replacement

Current Limitations

1) Inability to replicate in vitro differentiation protocols after implantation in vivo

2) Counteract the loss of MSC in vivo after implantation of in vitro generated tissue constructs

3) Failure to recapitulate in vivo conditions during development of engineered tissues in vitro

4) Propagation of cells under less than ideal conditions to reflect in vivo-improvements being made via hypoxia, serum-free, nutrients