Infantile Hypophosphatasia: Transplantation Therapy Trial Using Bone Fragments and Cultured Osteoblasts

Cahill, Richard A.; Wenkert, Deborah; Perlman, Sharon; Steele, Ann; Coburn, Stephen P.; McAlister, William H.; Mumm, Steven; Whyte, Michael P.

doi:10.1210/jc.2006-2131

Cited by 105 publications

(93 citation statements)

References 64 publications

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“…Two unrelated patients with worsening infantile HPP received marrow cell transplantations and survived a likely lethal outcome (Cahill et al 2007;Whyte et al 2003). Now, enzyme replacement therapy for severe HPP using human recombinant bone-targeted alkaline phosphatase provides promise for improved outcome (Whyte et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Outcome of Perinatal Hypophosphatasia in Manitoba Mennonites: A Retrospective Cohort Analysis

et al. 2013

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Hypophosphatasia (HPP) is the metabolic bone disease caused by loss-of-function mutation within the gene that encodes the "tissue nonspecific" isoenzyme of alkaline phosphatase (TNSALP). Perinatal HPP is usually fatal due to respiratory insufficiency, and infantile HPP often has a similar outcome although no formal study into the natural history of these severe forms of HPP has been undertaken. We reviewed our 80-year (1927-

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Section: Discussionmentioning

confidence: 99%

Outcome of Perinatal Hypophosphatasia in Manitoba Mennonites: A Retrospective Cohort Analysis

et al. 2013

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“…21,22 In hypophosphatasia, allogeneic bone marrow and/or MSC transplantation therapy has been reported by us and other groups. 4,14,23 However, the disease was not curable with these allo-transplantation therapies. In addition to the possible immunological rejection, allotransplantation is associated with some problems, such as infection and lack of appropriate donors.…”

Section: Discussionmentioning

confidence: 99%

Restoration of cellular function of mesenchymal stem cells from a hypophosphatasia patient

et al. 2009

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Mesenchymal stem cells (MSCs) can differentiate into multiple cell lineages and are used for regenerative treatments for a variety of diseases. However, the patient's cells cannot be used to treat genetic diseases. Allogeneic cells can serve as an alternative but long-term survival is uncertain. Our experience of allo-transplantation to a patient with hypophosphatasia, which is caused by mutations of the tissue non-specific alkaline phosphatase (TNSALP) gene resulting in low serum alkaline phosphatase (ALP) activity and skeletal deformity, did not improve these clinical characteristics. Therefore, we sought to use autologous MSCs for the treatment of hypophosphatasia. MSCs derived from the patient's bone marrow had a similar profile when compared with well-reported MSCs. However, the MSCs had extremely low ALP activity and could not produce a mineralized bone matrix even under the osteogenic culture conditions. We therefore transduced a retroviral vector with TNSALP promoter-driven TNSALP gene in the MSCs. In the culture condition, the MSCs had about 7-fold higher ALP activity than did mock-transduced MSCs, and showed mineralization as well as bone-specific markers. Furthermore, the MSCs, but not mock-transduced MSCs, newly formed bone at the frequency of 50% in nude rats. Transplantation of the TNSALP-transduced autologous MSCs might become a new therapy for hypophosphatasia.

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“…Donor bone fragments and marrow may be used to provide precursor cells to form TNSALP and replete osteoblasts that can improve bone mineralization (Cahill et al 2007). Initial engraftment with hematopoietic stem cells (HSCs) is done to avoid the potential problem of mesenchymal stem cell (MSC) rejection.…”

Section: Bone Marrow Transplantationmentioning

confidence: 99%

A concise review on hypophosphatasia with case report

Kaur

Nourabadi

Chavez

et al. 2016

IJM

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Hypophosphatasia (HPP) is an inherited dento-osseous metabolic disease characterized by inactivating mutations in the gene encoding the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP) which lead to a deficiency in TNSALP enzymatic activity. Low TNSALP activity results in increased levels of 3 known phosphocompound substrates: inorganic pyrophosphate (PPi), pyridoxal 5'-phosphate (PLP; the major circulating form of vitamin B6), and phosphoethanolamine (PEA). We discussed a systematic review with novel approach and a case report in which patient had multiple jaw reconstructive surgeries and early tooth loss in his childhood age but remained undiagnosed till his 60s. It should raise awareness among health care providers regarding low TNSALP and performing thorough etiological investigations which can ensure optimal clinical care and decision making for their patients by preventing complications like chondrocalcinosis, arthritis, early tooth loss, pseudo/complete fractures and pseudogout among the patients diagnosed with HPP even later in their life.

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Infantile Hypophosphatasia: Transplantation Therapy Trial Using Bone Fragments and Cultured Osteoblasts

Cited by 105 publications

References 64 publications

Outcome of Perinatal Hypophosphatasia in Manitoba Mennonites: A Retrospective Cohort Analysis

Outcome of Perinatal Hypophosphatasia in Manitoba Mennonites: A Retrospective Cohort Analysis

Restoration of cellular function of mesenchymal stem cells from a hypophosphatasia patient

A concise review on hypophosphatasia with case report

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