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Updated: Jul 14, 2026
Use of Human Perivascular Stem Cells for Bone Regeneration
Published on: May 25, 2012
Infantile hypophosphatasia: transplantation therapy trial using bone fragments and cultured osteoblasts
Richard A Cahill1, Deborah Wenkert, Sharon A Perlman
1Pediatric Research Institute, Cardinal Glennon Children's Hospitals, St. Louis, Missouri 63110, USA.
Insights
Marrow cell transplantation improved a patient with infantile hypophosphatasia (HPP), a rare bone disease. Donor cells engrafted into bone, forming alkaline phosphatase-producing osteoblasts and improving skeletal mineralization.
Area of Science:
- Regenerative Medicine
- Metabolic Bone Disease
- Alkaline Phosphatase Isoenzymes
Background:
- Hypophosphatasia (HPP) is a rare, inherited metabolic bone disorder caused by deficient tissue-nonspecific alkaline phosphatase activity.
- Infantile HPP presents with severe rickets, often leading to fatal respiratory complications within the first year of life.
- Currently, no established medical treatments exist for HPP.
Observation:
- A previous case showed improvement in a patient with life-threatening infantile HPP after marrow cell transplantation.
- Mouse models demonstrated potential benefits of bone fragment transplantation and cultured osteoblast-like cells.
Findings:
- A 9-month-old girl with infantile HPP received donor bone fragments and marrow cells.
- Radiographs showed improved skeletal mineralization after 4 months.
- Evidence of paternal DNA in recipient bone suggested donor cell engraftment, leading to improved mineralization and a milder clinical phenotype.
Implications:
- Marrow cell transplantation, including donor bone fragments, may offer a therapeutic strategy for HPP.
- Engraftment of donor precursor cells can form alkaline phosphatase-replete osteoblasts in the bone microenvironment.
- This approach holds promise for improving skeletal mineralization in HPP patients.
Background:
Hypophosphatasia (HPP) is a rare, heritable, metabolic bone disease due to deficient activity of the tissue-nonspecific isoenzyme of alkaline phosphatase. The infantile form features severe rickets often causing death in the first year of life from respiratory complications. There is no established medical treatment. In 1997, an 8-month-old girl with worsening and life-threatening infantile HPP improved considerably after marrow cell transplantation.
Objective:
Our aim was to better understand and to advance these encouraging transplantation results.
Design:
In 1999, based on emerging mouse transplantation models involving implanted donor bone fragments as well as osteoblast-like cells cultured from bone, we treated a 9-month-old girl suffering a similar course of infantile HPP.
Results:
Four months later, radiographs demonstrated improved skeletal mineralization. Twenty months later, PCR analysis of adherent cells cultured from recipient bone suggested the presence of small amounts of paternal (donor) DNA despite the absence of hematopoietic engraftment. This patient, now 8 yr old (7 yr after transplantation), is active and growing, and has the clinical phenotype of the more mild, childhood form of HPP.
Conclusions:
Cumulative experience suggests that, after immune tolerance, donor bone fragments and marrow may provide precursor cells for distribution and engraftment in the skeletal microenvironment in HPP patients to form tissue-nonspecific isoenzyme of alkaline phosphatase-replete osteoblasts that can improve mineralization.
