How mesenchymal stem cell cotransplantation with hematopoietic stem cells can improve engraftment in animal models

Murilo Montenegro Garrigós; Fernando Anselmo de Oliveira; Mariana Penteado Nucci; Leopoldo Penteado Nucci; Arielly da Hora Alves; Olivia Furiama Metropolo Dias; Lionel Fernel Gamarra

doi:10.4252/wjsc.v14.i8.658

How mesenchymal stem cell cotransplantation with hematopoietic stem cells can improve engraftment in animal models

World J Stem Cells. 2022 Aug 26;14(8):658-679. doi: 10.4252/wjsc.v14.i8.658.

Authors

Murilo Montenegro Garrigós^{1

2}, Fernando Anselmo de Oliveira¹, Mariana Penteado Nucci^{1

3}, Leopoldo Penteado Nucci⁴, Arielly da Hora Alves¹, Olivia Furiama Metropolo Dias¹, Lionel Fernel Gamarra⁵

Affiliations

¹ Hospital Israelita Albert Einstein, São Paulo 05652-900, São Paulo, Brazil.
² Instituto de Química, Universidade de São Paulo, São Paulo 05508-900, São Paulo, Brazil.
³ LIM44-Hospital das Clínicas, Faculdade Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil.
⁴ Centro Universitário do Planalto Central, Área Especial para Industria nº 02 Setor Leste - Gama-DF, Brasília 72445-020, Distrito Federal, Brazil.
⁵ Hospital Israelita Albert Einstein, São Paulo 05652-900, São Paulo, Brazil. lionelgamarra7@gmail.com.

Abstract

Background: Bone marrow transplantation (BMT) can be applied to both hematopoietic and nonhematopoietic diseases; nonetheless, it still comes with a number of challenges and limitations that contribute to treatment failure. Bearing this in mind, a possible way to increase the success rate of BMT would be cotransplantation of mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) to improve the bone marrow niche and secrete molecules that enhance the hematopoietic engraftment.

Aim: To analyze HSC and MSC characteristics and their interactions through cotransplantation in murine models.

Methods: We searched for original articles indexed in PubMed and Scopus during the last decade that used HSC and MSC cotransplantation and in vivo BMT in animal models while evaluating cell engraftment. We excluded in vitro studies or studies that involved graft versus host disease or other hematological diseases and publications in languages other than English. In PubMed, we initially identified 555 articles and after selection, only 12 were chosen. In Scopus, 2010 were identified, and six were left after the screening and eligibility process.

Results: Of the 2565 articles found in the databases, only 18 original studies met the eligibility criteria. HSC distribution by source showed similar ratios, with human umbilical cord blood or animal bone marrow being administered mainly with a dose of 1 × 10⁷ cells by intravenous or intrabone routes. However, MSCs had a high prevalence of human donors with a variety of sources (umbilical cord blood, bone marrow, tonsil, adipose tissue or fetal lung), using a lower dose, mainly 10⁶ cells and ranging 10⁴ to 1.5 × 10⁷ cells, utilizing the same routes. MSCs were characterized prior to administration in almost every experiment. The recipient used was mostly immunodeficient mice submitted to low-dose irradiation or chemotherapy. The main technique of engraftment for HSC and MSC cotransplantation evaluation was chimerism, followed by hematopoietic reconstitution and survival analysis. Besides the engraftment, homing and cellularity were also evaluated in some studies.

Conclusion: The preclinical findings validate the potential of MSCs to enable HSC engraftment in vivo in both xenogeneic and allogeneic hematopoietic cell transplantation animal models, in the absence of toxicity.

Keywords: Bone marrow transplantation; Co-transplantation; Engraftment; Hematopoietic reconstitution; Hematopoietic stem cells; Mesenchymal stem cells.