Stem cell homing in musculoskeletal injury

Abstract

The regenerative potential of injured adult tissue suggests the physiological existence of cells capable of participating in the reparative process. Recent studies indicate that stem-like cells residing in tissues contribute to tissue repair and are replenished by precursor bone marrow-derived cells. Mesenchymal stromal cells (MSC) are among the candidates for reparative cells. These cells can potentially be mobilized into the circulation in response to injury signals and exert their reparative effects at the site of injury. Current therapies for musculoskeletal injuries pose unavoidable risks which can impede full recovery. Trafficking of MSC to the injury site and their subsequent participation in the regenerative process is thought to be a natural healing response that can be imitated or augmented by enhancing the endogenous MSC pool with exogenously administered MSC. Therefore, a promising alternative to the existing strategies employed in the treatment of musculoskeletal injuries is to reinforce the inherent reparative capacity of the body by delivering MSC harvested from the patient's own tissues to the site of injury. The aim of this review is to inform the reader of studies that have evaluated the intrinsic homing and regenerative abilities of MSC, with particular emphasis on the repair of musculoskeletal injuries. Research that supports the direct use of MSC (without in vitro differentiation into tissue-specific cells) will also be reported. Based on accruing evidence that the natural healing mechanism involves the recruitment of MSC and their subsequent reparative actions at the site of injury, as well as documented therapeutic response after the exogenous administration of MSC, the feasibility of the emerging strategy of instant stem-cell therapy will be proposed.

Figure 1

Figure obtained from Granero-Moltó et al. (2009) with permission. MSC migrate to the fracture site in a time- and CXCR4-dependent manner. BLI was performed at days 1, 3, 7 and 14 after fracture/transplantation in mice with tibia fracture that received a transplant of either 10⁶ MSC-β-Act-Luc (MSC) (left panel), MSC-β-Act-Luc-CXCR4+ (CXCR4(+)) (middle panel), or MSC-β-Act-Luc-CXCR4-(CXCR4(−)) (right panel). Graded color bar indicates BLI signal intensity expressed as photons/seconds/cm²/steradian (sr).

Figure 2

Figure obtained from Hernigou et al. (2005) with permission. Marrow aspirates drawn from the patient were pooled and concentrated using the centrifugation method. The resulting concentrated buffy coat was reinjected intraosseously. Figure shows a trocar used for the reinjection which was positioned both in the nonunion gap and around the bone ends with the help of an image intensifier. The marrow was injected slowly at a rate of 20ml/min.

Figure 3

Figure obtained from Hernigou et al. (2005) with permission. Figure shows anteroposterior radiographs of a twenty-five-year-old patient who had sustained a type-I open fracture. The radiographs were made at the time of fracture (a) at the time of nonunion, before injection of autologous bone marrow (b) at one month after bone marrow injection, at which time the patient was allowed to begin partial weight-bearing (c) at two months after bone marrow injection (d) and at three months after bone marrow injection, at which time the external fixation was removed (e).