Promises and pitfalls of stem cell therapy for promotion of bone healing.
There is promise in combining stem cells with allogeneic bone matrix to promote bone healing. Murine bone marrow, peripheral blood, and compact bone cells were transplanted ectopically under the kidney capsule in mice, alone or in combination with allogeneic matrix products: powder and putty to determine their bone forming potential in comparison to transplanted femoral bone fragments and long-term cultured bone marrow cells. The end point was the amount of bone formed as determined by quantitative histology. Mononuclear cells from marrow, peripheral blood, or bone alone transplanted under the kidney capsule did not form bone. Mononuclear cell populations did not combine readily with matrix products and there was in vivo migration of the transplanted combinations. Kidney subcapsular transplanted cultured bone marrow cells formed bone in proportion to the culture period, but after 9 weeks, the extent was only 20% by area of that of similarly transplanted femoral bone fragments. An inductive stimulus for bone formation seemed necessary. Osteoprogenitor cells were not detected in significant numbers in blood unless high doses of cytokines were administered. A better definition of the optimal cell populations and manipulations required for promotion of bone healing is needed along with new (transplant) models that allow for cell tracking. Much work remains to overcome current pitfalls in the use of stem cells to promote allograft integration and bone healing.


METHODS
Therapeutic study, Level V (expert opinion). See the Guidelines for Authors for a complete description of levels of evidence.
Sharp
J Graham
JG
Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, 986395 Nebraska Medical Center, Omaha, NE 68198-6395, USA. jsharp@unmc.edu
Murphy
Barbara O'Kane
BO
Jackson
John D
JD
Brusnahan
Susan K
SK
Kessinger
Anne
A
Neff
James R
JR
D000818:Animals; D016026:Bone Marrow Transplantation; D016025:Bone Transplantation; D002478:Cells, Cultured; D005269:Femur / Q000637:transplantation*; D007668:Kidney; D051379:Mice; D009000:Monocytes / Q000166:cytology*; D010012:Osteogenesis / Q000502:physiology*; D033581:Stem Cell Transplantation; D014945:Wound Healing / Q000502:physiology*